The cellular response mediated by MHC class I restricted CD8+ T cells has been shown to be crucial in the control of Chagas disease. The K1 peptide derived from T. cruzi KMP-11 protein has a high binding affinity to the HLA-A*0201 molecule. Nevertheless, it is not known whether this peptide is processed and displayed as an MHC class I epitope during natural infection by T. cruzi. The aim of this study was to evaluate, by ELISPOT assay, the ability of K1 peptide to activate CD8+ T lymphocytes to produce IFN-gamma. Therefore, CD8+ T lymphocytes from 22 HLA-A*0201+ individuals, 12 chronic chagasic patients and 10 uninfected controls, were analysed. The results revealed that two of the chagasic patients had IFN-gamma-secreting CD8+ T cells that were able to respond to K1 peptide with a relative frequency of 110 and 230 per million CD8+ T cells. In contrast, none of HLA-A*0201+ uninfected controls responded to K1 peptide. Responses to HLA-A*0201 restricted peptide from the influenza matrix protein were found in six chagasic patients and four uninfected controls with an average frequency of 175 and 111 cells per million CD8+ T cells, respectively. Moreover, a flow cytometric assay for degranulation showed that chagasic responders had K1-specific cytotoxic CD8+ T cells. It is shown here for the first time that the K1 peptide is efficiently processed, presented and recognized by CD8+ T lymphocytes during the natural course of Chagas disease.

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Total nucleated cellularity and total erythroid cell populations were measured in spleen and bone marrow of mice at different times after treatment with 3 daily doses of T-2 toxin (2.0 mg/kg). It was found that the initial depletion of hematopoietic cells produced by the toxin was rapidly reverted in spleen, giving way after 48 hr to a significant hypercellularity which after 10 days was 2.5 times the normal levels, but this effect was not observed in bone marrow, which slowly recovered normal cellularity after 5 days. The cytological analysis revealed that there was a highly significant shift in the ratio of erythroid to non-erythroid cells, since erythroid cell populations increased by about 8-fold in spleen and nearly 2-fold in bone marrow between 10 and 35 days after intoxication. In order to test the integrity of the hematopoietic reserve capacity, a hemorrhagic stress was produced in intoxicated animals at 10-50 days after toxin exposure. It was found that the erythroid response capacity was significantly higher in the intoxicated animals compared to anemic controls. The results suggest that the initial cytotoxic damage produced by T-2 toxin in the hematopoietic system is followed by a significant erythroid hypercellularity, which can confer an increased capacity for response to a hemorrhagic emergency. Nat. Toxins 5: 152-156, 1997. 1997