MODULATION OF SPECIFIC T-CELL RESPONSES BY CONCURRENT INFECTION WITH LEISHMANIA-MAJOR AND LP-BM5 MURINE LEUKEMIA VIRUSES

C57BL/6 mice infected with a murine leukemia virus (MuLV) mixture desi gnated LP-BM5 develop an immunodeficiency syndrome termed MAIDS, chara cterized by a variety of T and B cell abnormalities, including elevate d levels of IgE, suggesting that IL-4 expression is increased in these animals. It has been suggested that the immunodeficiency associated w ith MAIDS is caused by a conversion of immune responses normally chara cterized by T(h)1 development towards a T(h)2-dominated response. Mice of the same strain, infected with Leishmania major, mount a protectiv e T(h)1 response with the induction of high levels of IFN-gamma and un detectable IL-4. We therefore infected mice with L. major at differing time points before and after virus infection and assessed the effects on T cell responsiveness, cytokine production and survival to L. majo r, as well as the effect on MAIDS-associated pathology. We have also i mmunized C57BL/6 mice with trinitrophenol-keyhole limpet haemocyanin ( TNP-KLH), which leads to a predominantly T(h)2 response, and compared the effects of MAIDS on the response to TNP-KLH with the effect of MAI DS on L. major infection, Our results show that significant immunodefi ciency with regard to infection by L. major is only apparent after 8 w eeks of LP-BM5 MuLV infection, by which time T and B cell defects are well advanced. Further, we have found that the strongly polarized T(h) 1 response stimulated by L. major infection can modulate the effect of MAIDS on T cells, leading to the survival of antigen-specific T cells , Our results suggest that the impairment of immune responses to eithe r TNP-KLH or L. major is due not to an alteration of the balance of T- h/T(h)2 subsets but to a general loss of reactivity in antigen-specifi c CD4(+) cells. However, prior activation of T(h)1 but not T(h)2 cells can inhibit the development of lymphoproliferation and immunodeficien cy caused by MAIDS.