GAMMA-DELTA T-CELLS AND THE IMMUNE-RESPONSE IN VISCERAL LEISHMANIASIS

Visceral leishmaniasis (VL) caused by Leishmania donovani, a protozoan parasite, is a disease of high morbidity associated with hepatosplenomegaly, hypergammaglobulinemia, fever and death. One of the immunological hallmarks of VL is a remarkable increase in serum immunoglobulin levels as a result of polyclonal B cell activation. This study demonstrated that T lymphocytes expressing the T cell receptors (TcR) gamma-delta in association with CD3 molecules are increased in circulation of patients with VL. A large proportions of TcR gamma-delta-bearing T cells had CD4+CD8- phenotype, and expressed CD25, CD38, CD71 and HLA-DR activation antigens. Furthermore, we demonstrated wide functional differences in TcR gamma-delta and TcR alpha-beta T cells in their proliferative response, secretion of interleukin-2 (IL-2), B cell growth factor (BCGF) and B cell differentiation factor (BCDF). It was of interest that the TcR gamma-delta T cells from patients with VL could be expanded by in vitro culture with human recombinant IL-2. Although these TcR gamma-delta T cells secreted diminished levels of IL-2, they produced highly augmented levels of both BCGF and BCDF, suggesting that secretion of these lymphokines in these T cell subsets is regulated independently. The relative increases in the CD4+ CDw29+ TcR gamma-delta T cell subsets and their secretion of highly elevated levels of BCGF and BCDF largely accounted for the humoral immune system abnormality and hypergammaglobulinemia found in this disease. These observations may help to explain that TcR gamma-delta T cells might be functional in vivo and are involved in immunological mechanisms of pathogenesis in VL.