title: Modulation of specific T cell responses by concurrent infection with Leishmania major and LP-BM5 murine leukemia viruses.
abstract: C57BL/6 mice infected with a murine leukemia virus (MuLV) mixture designated LP-BM5 develop an immunodeficiency syndrome termed MAIDS, characterized by a variety of T and B cell abnormalities, including elevated levels of IgE, suggesting that IL-4 expression is increased in these animals. It has been suggested that the immunodeficiency associated with MAIDS is caused by a conversion of immune responses normally characterized by Th1 development towards a Th2-dominated response. Mice of the same strain, infected with Leishmania major, mount a protective Th1 response with the induction of high levels of IFN-gamma and undetectable 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. major, as well as the effect on MAIDS-associated pathology. We have also immunized C57BL/6 mice with trinitrophenol-keyhole limpet haemocyanin (TNP-KLH), which leads to a predominantly Th2 response, and compared the effects of MAIDS on the response to TNP-KLH with the effect of MAIDS on L. major infection. Our results show that significant immunodeficiency with regard to infection by L. major is only apparent after 8 weeks of LP-BM5 MuLV infection, by which time T and B cell defects are well advanced. Further, we have found that the strongly polarized Th1 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 either TNP-KLH or L. major is due not to an alteration of the balance of Th1/Th2 subsets but to a general loss of reactivity in antigen-specific CD4+ cells. However, prior activation of Th1 but not Th2 cells can inhibit the development of lymphoproliferation and immunodeficiency caused by MAIDS.
authors.affiliation: Department of Immunology, DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, CA 94304, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Doherty
authors.forename: H C
authors.initials: HC
authors.lastname: Morse
authors.forename: R L
authors.initials: RL
authors.lastname: Coffman
mesh_terms: D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000150:complications / Q000276:immunology*; D009052:Leukemia Virus, Murine; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
chemical_list: D007371:Interferon-gamma