Moreover, combination therapy using cisplatin and human leucocyte antigen-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 in patients with advanced or recurrent adenocarcinoma of the stomach showed that the disease control rate (partial and stable disease) was 100% after two cycles of the combination therapy [25]. Delayed-type hypersensitivity response to leishmanial antigens has been widely used to assess the level of host protection to the disease [26]. It has been well established that induction of a DTH response is mediated via Th1 cell as it secretes IFN-γ which

is expressed during macrophage stimulation check details for parasite killing [27]. The DTH responses to leishmanin were apparent during L. donovani infection in BALB/c mice as evident by an increase in the foot pad swelling after injection of leishmanin. The increase was much higher when the animals were treated with immunochemotherapy than the groups SB203580 of animals treated with

chemotherapy or immunotherapy alone. This suggests that the mice treated with cisplatin + 78 kDa with or without adjuvant (MPL-A) developed a strong cell-mediated immune response indicating that drug treatment followed by vaccine therapy was helpful in reversal of immunosuppression caused by the parasite. Earlier studies from our laboratory reported an increased DTH response in animals treated with low dose of cisplatin [14]. Correlation between DTH responses and parasite load has also been reported [14, 15]. This was evident from our results where a strong positive correlation was observed between enhanced DTH response and reduced parasite load. The immunological response was further characterized by analysing the

distribution of IgG1 and IgG2a specific antibodies in the serum samples of infected and treated BALB/c mice. Production of IgG2a is normally associated with IFN-γ secretion and the development of a Th1 immune response. However, in contrast, production of the IgG1 is normally associated with IL-4 secretion and the development of Th2 type of response. The treated animals revealed higher IgG2a and lower IgG1 levels than the infected controls. However, maximum levels of IgG2a and minimum levels of IgG1 were observed in animals Clomifene treated with cisplatin + 78 kDa + MPL-A than those animals that are treated with cisplatin alone or 78 kDa/78 kDa + MPL-A alone. It has been shown earlier from our laboratory that immunization of mice with 78 kDa + MPL-A resulted in significant increase in IgG2a response [6]. Moreover, a significant reduction in specific antibody titres was observed after treatment with immunochemotherapy (Glucantime + Leish-110f/MPL-SE) in dogs suffering from canine leishmaniasis [18]. Th1 and Th2 cell lymphocytes are important mediators in generating immunity to leishmaniasis and can be distinguished by the cytokines they secrete.

Importantly, simulated LipCl2MDP depletes inflammatory DCs and tolerogenic DCs with equal potency, with sustained protection arising through the dynamic regulation of these DC subsets under conditions of reduced inflammation. The up-regulation of tolerogenic DCs also contribute to the simulated anti-CD3 mediated efficacy in diabetic NOD mice [102], which is again characterized by the return of an apparently benign cellular infiltrate Ponatinib [103]. In the case of anti-CD3, other mechanisms (e.g. induction of regulatory T cells) also contribute to sustained remission. The decision to represent a tolerogenic

DC phenotype illustrates how the broader immunology state-of-knowledge was brought to bear in reconciling NOD mouse results with LDE225 the reported underlying biology. Conversely, it illustrates a gap in understanding based on available NOD mouse data and an area where additional data on NOD DCs could clarify the mechanistic underpinnings of these therapies. By selecting internal validation experiments that targeted

different biological components, the virtual mouse was fine-tuned along multiple biological axes, yielding a single parameterization that reproduces a wide array of behaviours. By itself, this was a non-trivial and insightful exercise. Furthermore, external validation experiments were selected to assess the virtual mouse response to distinct stimuli, thereby indicating whether fine-tuning is a necessary prerequisite in the simulation of an appropriate response. The virtual mouse reproduced outcomes accurately for 21 of 24 experiments, representing five interventions. This generally positive result suggests that the virtual mouse could be a valuable Exoribonuclease counterpart to experimental investigations into novel therapeutic strategies (assuming the main mechanisms of action are within the scope of the modelled biology). The mismatches highlighted disparities in the published anti-CD40L data set that we had not appreciated previously. However, the potential importance of dose and

timing to outcomes, which were observed in the simulations, is entirely consistent with their importance in the experimental data, as highlighted in our 2004 review [1]. The model could, plausibly, be used to design experiments to reconcile disparate data. Additionally, dose/timing sensitivity argues that research efforts should use virtual mice whose disease progression (e.g. timing of diabetes onset) is aligned with the experimental mice and should evaluate a range of doses/timing to account for variability inherent in the data (i.e. NOD mouse colonies with variability in rate of disease progression) used to generate the model. While this model is intended to broadly support research efforts in the field of type 1 diabetes, like any other model it has limitations.

Recently, a subset of IL-17-producing T cells (Th17) distinct

from Th1 or Th2 cells has been described and shown to be crucial in induction of autoimmune tissue injury [34]. Th17 response has been linked to the pathogenesis of diseases such as multiple sclerosis, psoriasis, rheumatoid arthritis, colitis, autoimmune encephalitis [35] and leishmaniasis [36]. Although a recent study has suggested a protective role for IL-17 in experimental T. cruzi PDE inhibitor infection [37], considering the pathogenic nature of this cytokine in human diseases, it is possible that it plays a role in Chagas disease-associated pathology. In our study we observed that captopril, in the presence of T. cruzi, increased the frequency of CD4+IL-17+ T cells and that this effect was impaired when cells were treated with HOE-140, a B2R antagonist. Interestingly, infection in association with captopril led to a decrease of selleck screening library IL-17 expression by CD8+ T cells, which was not affected by treatment with HOE-140.

Considering that IL-17 expression by CD4+, but not CD8+ T cells, is impaired by HOE-140 in our model, we may surmise that BK2R is probably involved in IL-17 induction by captopril. Of interest in this context, studies in BALB/c mice infected by the periodontal pathogen Porphyromonas gingivalis linked Th17 and Th1 responses to pathogen-induced activation of the BK2R pathway [38]. In a myosin-induced experimental

autoimmune myocarditis, A/J mice were immunized and treated orally with captopril, which ameliorated autoimmune myocarditis as measured by the reduction in cardiac hypertrophy and the incidence and severity of inflammation, necrosis and fibrosis [26]. Captopril also reduced in vivo cell-mediated inflammatory responses based upon the observed reduction of myosin-specific delayed-type hypersensitivity in antigen-immunized mice. However, these effects were not due to a direct effect on T cells as these cells proliferated normally and the level of secreted cytokines was unaltered [26]. Of note, however, IL-17 levels were not evaluated in that study. In summary, our results suggest that captopril might interfere with host–parasite equilibrium by enhancing infection of monocytes, decreasing the expression BCKDHA of the modulatory cytokine IL-10, while guiding development of the proinflammatory Th17 subset. Further studies are under way to investigate the effects of captopril in the immune response of chronic chagasic patients and whether this would influence pathology development. This work was supported by CNPq, INCT-DT and FAPEMIG. C. A. S. M., L. M. D. M., J. S., K. J. G. and W. O. D. are CNPq fellows; J. S. C. S. and F. A. V. are CAPES fellows. The authors do not have any conflict of interest with the material presented in the paper.

Apoptosis was especially reduced in CD4+CD25hi cells after restimulation with the nematode somatic antigen or studied fractions. In comparison with DEX, markedly fewer cells underwent apoptosis when exposed to rTNF-α (Figure 6). The subpopulation of CD3+CD4+ and CD+CD25hi lymphocytes both from naïve and infected

mice responded very weakly: the reduction in the percentage of apoptotic CD3+CD4+ cells of naïve mice was observed when AgS or fractions F9, F13 were added. After the exposition of CD4+CD25hi cells to AgS, fractions F9 or F13 the percentage of apoptotic cell increased, whereas F17 reduced apoptosis. Only CD3+CD8+ cells of infected mice survived better upon H. polygyrus antigen stimulation, and apoptosis was inhibited by AgS, F9 and F13. Fraction F9 significantly reduced apoptosis of CD8+ cells; to 8% after restimulation compared with the control sample. Fraction F17 induced MG 132 an opposite effect to other fractions in all examined T-cell populations stimulated to apoptosis by rTNF-α; CD4+CD25hi and CD3+CD4+ cells were supported to survive

and only 10% of these cells were apoptotic. The same fraction restored apoptosis of CD3+CD8+ cells to the control level. The difference in activity of antigenic fractions were recognized mainly between F9 and F17 and examined cell populations responded distinctly to H. polygyrus somatic antigen fractions; the most sensitive cell population was CD4+CD25hi after exposure to DEX and CD3+CD8+ T cells after exposure to rTNF-α. The exposition of cells in vitro to H. polygyrus antigen RAD001 purchase resulted in changes in the percentage of Bcl-2-positive T cells in all examined subpopulations: CD3+CD4+, CD4+CD25hi and CD3+CD8+ (Figure 7). Infection and restimulation of CD3+CD4+ lymphocytes with the nematode antigen and all examined fractions increased the percentage of Bcl-2-positive cells and reached 65% in uninfected mice and 80% in infected mice. After

stimulation with AgS, F9 and F13, the percentage of CD4+CD25hi Bcl-2-positive cells in naïve mice decreased, but in infected mice achieved the control level, however, was still higher than in cells primary exposed to antigens in vitro. Infection with H. polygyrus increased the percentage of Bcl-2-positive CD4+ cells and restimulation of CD4+CD25hi with parasitic learn more antigens restored the percentage to the control level for that cell population. In contrast, infection with H. polygyrus reduced the percentage of CD3+CD8+ Bcl-2-positive cells from above 80% in naïve mice to <20% in infected mice. The effect was enhanced by the nematode antigen and all antigenic fractions. FLIP appeared in cells isolated from infected mice (Figure 8). Heligmosomoides polygyrus antigen and its fractions with antiapoptotic activity increased FLIP expression both in cells of naïve, control mice and mice infected with the nematode.

It is noteworthy that the participation of CCL20 in IL-17+ γδ T-cell migration during allergy cannot be ruled out. The fact that CCL20 neutralization slightly diminished IL-17+ γδ T-cell chemotaxis toward OPW suggests that CCL20/CCR6

and CCL25/CCR9 might cooperate for their attraction to the allergic site. Even though the CCR9/α4β7 expression determines a phenotype of intestinal mucosa population [[18]], we detected the presence of CCR9+/α4β7+ lymphocytes in the pleura during the allergic response. It has been demonstrated that CCL25 induces T-cell adhesion via α4β7 integrin [[17]] and preferentially induces the migration of α4β7+ T cells via CCR9 [[36]]; even though the mechanisms involved in this phenomenon remain to be elucidated. γδ T cells express several GDC-0449 mouse integrins, such α4β1 and α4β7, which are known to be important for the adhesion to the endothelium and transmigration into inflamed tissue [[22, 23, 37-39]]. Indeed, selective blocking mAbs against α4β1 integrin inhibited human γδ T-lymphocyte adhesion to cytokine-activated AZD2014 concentration endothelial cells [[24]]. Moreover, CCL25 has been shown to induce T lymphocyte adhesion via the interaction of α4β7 and α4β1 integrins to MadCAM-1 and VCAM-1, respectively [[16, 17]]. These data corroborate

our findings that CCL25 induced the transmigration of γδ T lymphocytes through endothelial cells, via the interaction of α4β7 integrin to MadCAM-1/VCAM-1. During allergy, the expression of VCAM-1 (but not ICAM-1) by mouse endothelium has been shown to be upregulated [[40]]. In addition, the Sclareol in vitro stimulation of HUVECs by the Th2 cyto-kine IL-4 also induced the expression of VCAM-1, failing to alter ICAM-1 expression [[41]], which is in accordance with our observations that IL-4 triggered increased expression

of VCAM-1 and MadCAM-1 on mouse endothelial cells, but not of ICAM-1 (not shown). Previous reports have shown the importance of the α4 integrin chain for the in vivo migration of T lymphocytes that are shown to preferentially migrate via α4 integrin/VCAM-1 pathway rather than via αLβ2 or ICAM-1 [[40, 42]]. However, no data specifically concerned the role of α4β7 integrin on γδ T-lymphocyte migration during an allergic response. Our results demonstrate the relevance of α4β7 integrin for γδ T-cell migration during an allergic reaction, which was reinforced by the fact that the ex vivo blockade of α4 chain impaired the migration of adoptively transferred CFSE+ γδ T lymphocytes into the allergic site. Moreover, we observed that αLβ2 blockade failed to inhibit γδ T lymphocyte in vitro transmigration toward OPW (not shown). It is also noteworthy that OVA immunization induced a sevenfold increase on the numbers of γδ T cells expressing α4β7 integrin in the spleen (not shown).

“
“Magnetic resonance imaging (MRI) cerebral microbleeds

(CMB) arise from ferromagnetic haemosiderin iron assumed to derive from extravasation of erythrocytes. Light microscopy of ageing brain frequently reveals foci of haemosiderin from single crystalloids to larger, predominantly perivascular, aggregates. The pathological and radiological relationship between these findings is not resolved. Haemosiderin deposition SRT1720 in vivo and vascular pathology in the putamen were quantified in 200 brains donated to the population-representative Medical Research Council Cognitive Function and Ageing Study. Molecular markers of gliosis and tissue integrity were assessed by immunohistochemistry in brains with highest (n = 20) and lowest (n = 20) levels of putamen haemosiderin. The association between haemosiderin counts and degenerative and vascular brain Metabolism inhibitor pathology, clinical data, and the haemochromatosis (HFE) gene H63D genotype were analysed. The frequency of MRI CMB in 10 cases with highest and lowest burden of putamen haemosiderin, was compared using post mortem 3T MRI. Greater putamen haemosiderin was significantly associated with putaminal indices of small vessel ischaemia (microinfarcts, P < 0.05; arteriolosclerosis, P < 0.05; perivascular attenuation, P < 0.001) and with lacunes in any brain region (P < 0.023) but not large vessel disease, or

whole brain measures of neurodegenerative pathology. Higher levels of putamen haemosiderin correlated with more CMB (P < 0.003). The MRI-CMB concept should take account of brain iron homeostasis, and small vessel ischaemic change in later life, rather than only as a marker for minor episodes of cerebrovascular extravasation. These data are of clinical relevance, suggesting that basal ganglia MRI microbleeds may be a surrogate for ischaemic small vessel disease rather than exclusively a haemorrhagic diathesis. "
“J. Attems, A. Thomas and K. Jellinger (2012) Neuropathology and Applied Neurobiology38,

582–590 Correlations between cortical and subcortical tau pathology Aim: Recent studies indicate that tau pathology in Alzheimer’s disease (AD) does not initially manifest in the cerebral cortex but in selected Oxalosuccinic acid subcortical nuclei, in particular the locus ceruleus (LC). In this study we correlate both olfactory and brainstem tau pathology with neuritic Braak stages. Methods: We examined 239 unselected autopsy cases (57.3% female, 42.7% male; aged 55–102, mean 82.8 ± 9.7 SD years; AD, 44.8%; non-demented controls, 31.8%; Parkinson’s disease, 5.0%; dementia with Lewy bodies, 2.5%; AD + Lewy body disease, 15.9%). Neuropathological examination according to standardized methods included immunohistochemistry and semiquantitative assessment of tau lesions in LC, substantia nigra (SN), dorsal motor nucleus of nervus vagus (dmX), and olfactory bulb (OB). Results: In Braak stage 0, tau pathology (usually very sparse pretangle material) was seen in the OB in 52.

Presumably, TLR2 is activated by a component(s) of S. aureus located at the cell wall, such as lipoproteins and lipopeptides11–17 with some controversies as to their role as a ligand for human TLR2,18 to transmit a signal

leading to the phosphorylation Ferroptosis inhibitor review of JNK and the subsequent inhibition of superoxide production in macrophages. In the present study, we took a genetic approach to search for additional bacterial components required for the exploitation of TLR2 by S. aureus and obtained evidence that genes responsible for the synthesis of d-alanylated wall teichoic acid (WTA) play a crucial role in this exploitation. An antibody (#9251) specifically recognizing the phosphorylated form of JNK and another (#9252) recognizing both the phosphorylated and unphosphorylated forms were purchased from Cell Signaling Technology (Beverly, MA). Using these antibodies, two isoforms of JNK with relative molecular mass (Mr) values of 46 000 and 54 000 MW and their

phosphorylated forms were detectable. pHY300PLK, an Escherichia coli–S. aureus shuttle vector containing a tetracycline-resistant gene, was obtained from Takara-Bio (Ohtsu, Japan). Fluorescein isothiocyanate was purchased from Molecular Probes (Eugene, OR); the synthetic lipopeptide tripalmitoyl-S-glycerylcysteine (Pam3Cys), lipopolysaccharide (LPS) from Salmonella enteritidis, and N-acetyl-l-cysteine were from Sigma-Aldrich (St Louis, MO); mannitol salt agar medium was from Nissui (Tokyo, Japan); Diogenes was from National buy FK228 Diagnostics (Atlanta, GA); and the Dual Luciferase Assay kit was from Promega Corp. (Madison, WI). Cell surface mutants of S. aureus are derivatives of the parental wild-type S. aureus strain RN4220 (a derivative of NCTC8325-4, a restriction and agr mutant)19 (Table 1). To construct the mutant Molecular motor strains M0614 and M0615, sequences corresponding to portions of the SA0614 and SA0615 genes (nucleotide positions 50–400 and 32–507, respectively, with

the first nucleotide of the translation start codon numbered 1) were amplified by polymerase chain reaction (PCR) and inserted into the S. aureus integration vector pSF151.20 RN4220 was then transformed with the resulting plasmids pSFSA0614 and pSFSA0615, and M0614 and M0615 where the cognate genes had been disrupted by homologous recombination were selected. RN4220 and all the mutant strains were grown in Luria–Bertani medium at 37° (except for M0702 which was grown at 30°) to full growth, washed once with phosphate-buffered saline (PBS), and used in the subsequent experiments. Macrophages from the peritoneal cavity of thioglycollate-injected C57BL/6 mice were prepared and maintained in RPMI-1640 medium supplemented with 10% [volume/volume (v/v)] heat-inactivated fetal bovine serum at 37° with 5% (v/v) CO2 in air.21 Mice carrying disrupted tlr2 in a C57BL/6 background22 were provided by Dr Shizuo Akira of Osaka University.

27 Cardiovascular disease is the leading cause of death in both dialysis and transplant patients, and current evidence suggests caution with the use of both agents but favours the utilization of pioglitazone if a PPARγ agonist was desired. These agents, which include acarbose, miglitol and voglibose, are enzyme inhibitors that act in the intestines to attenuate the absorption of carbohydrates. Acarbose has been shown to reduce HbA1c by approximately 0.8% in type 2 diabetics,3 although the increased delivery of carbohydrates into the colon means gastrointestinal side effects are very Palbociclib datasheet common and include flatulence,

bloating, abdominal pain and diarrhoea. This severely limits the utility of these agents as between 24% and 45% of patients will discontinue these agents.3,28 In the context of renal impairment, acarbose is not recommended for use in individuals with an eGFR less than 25 mL/min, although it is often overlooked for any degree of renal insufficiency. Its use in kidney transplant recipients is also likely to be prohibited as its concomitant use with mycophenolate mofetil could trigger gastrointestinal upset. The meglitinides, repaglinide and netaglinide, are short-acting Kinase Inhibitor Library order agents that close the ATP-dependent

potassium channel on cell membranes of the pancreatic beta cell in a similar fashion to sulphonylureas, Sodium butyrate resulting in depolarization of cells and subsequent calcium influx inducing insulin secretion. By administration pre-meals, it reduces postprandial glycaemia and is associated with HbA1c reductions of up to 2.1% (repaglinide > netaglinide).29 Side effects of the meglitinides include hypoglycaemia and weight gain, with gastrointestinal

symptoms rare. One of the significant advantages of meglitinides is the safe administration of these agents in the context of even severe renal impairment (repaglinide > netaglinide), as these drugs undergo hepatic clearance. To this effect, repaglinide is one of the only drugs shown to be safe (minimal interaction with immunosuppression) and efficacious (HbA1c lowering) post-transplantation30 and is considered the first-line agent for use in the context of new onset diabetes after transplantation.2 The two main gut hormones (or incretins) are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), secreted by K cells in the upper small intestines. Gut hormones have been shown to have an important role in whole-body glucose homeostasis by suppressing meal-related glucagon secretion, delay gastric emptying and induce satiety,31 with GLP-1 having greater potency than GIP.

To distinguish between these two possibilities, we directly investigated whether constitutive activation of Btk had the capacity to change the B-cell U0126 in vivo fate in the 3-83μδ Tg system. The 3-83μδ Tg encodes an antibody specific for MHC class I of the H-2Kk,b haplotype 29. On a non-autoreactive background, the expression of the 3-83μδ BCR commits B cells to the follicular or MZ subsets in the spleen. In these 3-83μδ BCR Tg mice only B cells that have edited their BCR are able to differentiate into

CD5+ B-1 B cells: all peritoneal B220lowCD5+ B-1 B cells have lost the 3-83μδ BCR specificity detected by the 54-1 anti-idiotypic antibody (Fig. 4A). We generated 3-83μδ Tg E-Btk-2 and EY-Btk-5 mice on the non-autoreactive H2-Kd background. As expected, in the spleen of these mice all conventional B220highCD5− B cells had high 54.1 reactivity. However, B220lowCD5+ B cells had lost their 54.1 reactivity (Fig. 4B), while surface Ig μ and κ expression levels were similar (data not shown). These results indicate that 3-83μδ Tg E-Btk-2 and EY-Btk-5 B220lowCD5+ B-1 B cells in the spleen had undergone receptor editing. We therefore conclude that the presence of the E-Btk-2

or EY-Btk-5 Tg did not change the follicular versus Protein Tyrosine Kinase inhibitor B-1 B-cell subset choice. Instead, the increased proportions of splenic CD5+ B cells in E-Btk-2 and EY-Btk-5 mice most likely resulted from increased expansion or survival of B-1 B cells. The presence of the E-Btk-2 and EY-Btk-5 Tg also did not change the MZ B-cell subset choice in VH81X Tg mice, which carried a VH81X Tg encoding an Ig heavy chain favoring MZ B-cell development 30. As shown in Fig. 5A and B cells recognized by the 35-1 anti-idiotypic antibody are efficiently selected into the MZ B-cell compartment

in VH81X WT, but not in VH81X Tg Btk-deficient spleens (Fig. 5B). Splenic 35-1+ CD19+ B cells from VH81X E-Btk-2 Tg mice expressed similar CD5 levels as those from VH81X WT, lacked the B220low phenotype characteristic for CD5+ B cells and, importantly, had a CD21high/CD23low MZ phenotype similar to those of VH81X WT mice (Fig. 5A). filipin Moreover, in contrast to E-Btk-2 mice (which had few MOMA-1+ macrophages and no MZ B cells in the spleen), in E-Btk-2 mice that carried a VH81X Tg splenic architecture was corrected: EY-Btk-2 VH81X double Tg spleens contained IgM+ B cells within and outside rims of brightly staining MOMA-1+ macrophages (Fig. 5A; right panels). Collectively, these findings show that MZ cell fate was maintained in the presence of constitutive active Btk, indicating that the VH81X BCR specificity is dominant over the increased BCR signal strength generated by the E-Btk-2 Tg.

berghei infection. Increased expression of ECM components was observed in thymi from infected mice. In contrast, down-regulated surface expression of fibronectin and laminin receptors was observed in thymocytes from these animals. Moreover, in thymi from infected mice there was increased CXCL12 and CXCR4, and a decreased expression of CCL25 and CCR9. An altered thymocyte migration towards ECM elements

and chemokines was seen when the thymi from infected mice were analysed. Evaluation of ex vivo migration patterns of CD4/CD8-defined thymocyte subpopulations revealed that double-negative (DN), and CD4+ and CD8+ single-positive (SP) cells from P. berghei-infected mice have higher migratory responses compared with controls. Interestingly, Ixazomib solubility dmso increased numbers of DN and SP subpopulations were found in the spleens of infected mice. Overall, we show that the thymic atrophy observed in P. berghei-infected mice is accompanied by thymic microenvironmental changes that comprise altered expression of thymocyte

migration-related HDAC inhibitor molecules of the ECM and chemokine protein families, which in turn can alter the thymocyte migration pattern. These thymic disturbances may have consequences for the control of the immune response against this protozoan. The immune response during malaria is highly complex; this is partially the result of the intricate molecular structure of Plasmodium sp., the aetiological agent of the disease. This protozoan stimulates multifaceted immune responses, including antibodies, natural killer (NK) and NKT cells, and CD4+ and

CD8+ T cells.1,2 The immune response to the intraerythrocytic stages of the parasite has been better characterized by the use of murine experimental models. In this stage the CD4+ T helper type 1 response is essential for the development of the next events of the immune response in experimental malaria.3,4 We previously reported that the thymus gland is also a target organ in Plasmodium berghei infection: P-type ATPase there is atrophy with depletion of CD4+ CD8+ double-positive (DP) thymocytes, and histological alterations with loss of delimitation between the cortical and medullar regions. Moreover, we detected the intrathymic presence of parasites.5 The thymus is a primary lymphoid organ, responsible for the differentiation of T lymphocytes, including the shaping of an appropriate T-cell repertoire. This process is controlled by the cells and molecules of the thymic microenvironment, a tri-dimensional network essentially formed by epithelial cells, together with small numbers of dendritic cells, macrophages and fibroblasts.