The role of CD4 T cells in the pathogenesis of murine AIDS.
LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD154 on CD4 T cells with CD40 on B cells. However, it is not clear which additional characteristics of the phenotypically and functionally heterogeneous CD4 T-cell compartment are required. Here, in vivo adoptive transfer experiments using B6.nude recipients are employed to compare the pathogenic abilities of CD4 T-cell subsets defined on the basis of cell surface phenotypic or functional differences. Th1 and Th2 CD4 T cells equally supported MAIDS induction. The rare Thy1.2(-) CD4 subset that expands upon LP-BM5 infection was not necessary for MAIDS. Interestingly, CD45RB(low) CD4 T cells supported significantly less disease than CD45RB(high) CD4 T cells. Because the decreased MAIDS pathogenesis could not be attributed to inhibition by CD45RB(low) CD25(+) natural T-regulatory cells, an intrinsic property of the CD45RB(low) cells appeared responsible. Similarly, there was no evidence that natural T-regulatory cells played a role in LP-BM5-induced pathogenesis in the context of the intact CD4 T-cell population.
Li
Wen
W
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Green
William R
WR
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D017493:Leukocyte Common Antigens; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D016183:Murine Acquired Immunodeficiency Syndrome / Q000209:etiology*; D012190:Retroviridae / Q000472:pathogenicity; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000821:virology; D018417:Th1 Cells / Q000821:virology; D018418:Th2 Cells / Q000821:virology
D017493:Leukocyte Common Antigens