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: T M Doherty, H C Morse 3rd, R L Coffman
• Journal: International immunology (Int Immunol) Vol. 7 Issue 1 Pg. 131-8 (Jan 1995) ISSN: 0953-8178 [Print] England
• PMID: 7718509 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interferon-gamma

Topics

• Animals
• Female
• Interferon-gamma (biosynthesis)
• Leishmania major
• Leishmaniasis, Cutaneous (complications, immunology)
• Leukemia Virus, Murine
• Lymphocyte Activation
• Male
• Mice
• Mice, Inbred C57BL
• Murine Acquired Immunodeficiency Syndrome (complications, immunology)
• T-Lymphocyte Subsets (immunology)
• Th1 Cells (immunology)
• Th2 Cells (immunology)
• Time Factors