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Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP-11) is able to induce protective immunity in mice. In humans, T-cell immunity during Chagas disease has been documented using parasite antigens allowing the identification of specific CD8+ T cells. However, little is known about the CD4+ T-cell response during the evolution of the disease. In this paper, the induction of a natural CD4+ T-cell response against the KMP-11 protein in T. cruzi infected humans was studied to assess whether this parasite-derived protein could be processed, presented and detected as a major histocompatibility complex class II restricted epitope. The results show that helper T cells from 5 out of 13 chagasic patients specifically produced interferon-γ after exposure to the KMP-11 antigen, whereas healthy donors and non-chagasic cardiopathic patients did not respond. This is the first description of T. cruzi KMP-11 protein recognition by CD4+ T cells in chronic chagasic patients.Immunology and Cell Biology (2009) 87, 149–153; doi:10.1038/icb.2008.76; published online 28 October 2008 [ABSTRACT FROM AUTHOR]

The mechanism behind the apparent lack of effective antiviral immune responses in chronic hepatitis C virus (HCV) patients is poorly understood. It remains unclear if natural regulatory T cells (Treg) contribute to the induction and maintenance of HCV persistence. We herein report for the first time that CD25highIFN-γ−FOXP3high Tregs can be rapidly induced by culturing peripheral blood mononuclear cells (PBMCs) of HCV-positive patients with HCV protein-derived peptides. The HCV-specific Tregs, generally CD4+CD45RO+, did not proliferate in response to HCV peptide and failed to produce interferon (IFN)-γ, in distinct contrast to antiviral effector cells. Stimulation of healthy donor PBMCs with HCV peptides did not result in CD25 and FOXP3 upregulation above non-antigen background. To further investigate the antigen specificity of these potentially disease-associated natural Tregs, CD25+ cells were isolated from PBMCs, labeled with carboxyfluorescein diacetate succinimidylester and added back to CD25-depleted PBMCs, and the co-cultures were then stimulated with individual peptides derived from the HCV core protein. We found that the actual peptide that can stimulate Treg varied between patients, but within any given subject only a small number of the peptides were able to stimulate Treg, suggesting the existence of dominant Treg epitopes. Although functional experiments for these peptides are ongoing in our laboratory, data presented here suggests that HCV-specific natural Tregs are abundant in infected individuals, in contrast to the extremely low frequency of anti-HCV effector T cells, supporting the view that natural Treg may be implicated in host immune tolerance during HCV infection.Immunology and Cell Biology (2007) 85, 197–204. doi:10.1038/sj.icb.7100020; published online 2 January 2007 [ABSTRACT FROM AUTHOR]