Both naive and memory CD4 T cell subsets become anergic during MAIDS and each subset can sustain disease.
Infection of C57BL/6 mice with the LP-BM5 mixture of retroviruses causes a severe murine acquired immunodeficiency syndrome (MAIDS). After infection, the entire CD4 T cell population shifts to a memory/activated phenotype and the CD4 cells become anergic to further stimulation. This drastic shift in phenotype could result either from a response of naive cells to the virus or its products and/or from the selective expansion of cells already having a memory phenotype. We have investigated whether both naive and memory CD4 T cells can be anergized during BM5 infection and whether each subset is sufficient for disease development. We show that V beta 3/V alpha 11 TCR transgenic mice that have > 98% CD4 T cells with naive phenotype develop MAIDS. Their spleens and lymph nodes become enlarged, their CD4 population expressing the TCR transgene shifts to a memory/activated phenotype, and the CD4 cells neither proliferate nor secrete IL-2 in response to specific Ag, a fragment of pigeon cytochrome C, or to mitogens. Adult thymectomized mice, having memory but not naive CD4 T cells, also developed MAIDS and anergy of the CD4 T cell population at a rate and extent comparable to normal control mice. Furthermore, CD4 T cells from mice primed with keyhole limpet hemocyanin 6 wk before infection with BM5 also became unresponsive to KLH during MAIDS. Thus, both naive and memory CD4 T cells are rendered anergic by the BM5 virus infection and it is likely that each subset is sufficient to sustain the development of MAIDS.
Koch
S
S
Department of Biology, University of California, San Diego, La Jolla 92093.
Muralidhar
G
G
Swain
S L
SL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013934:Thymectomy