Murine AIDS requires CD154/CD40L expression by the CD4 T cells that mediate retrovirus-induced disease: Is CD4 T cell receptor ligation needed?
LP-BM5, a retroviral isolate, induces a disease featuring an acquired immunodeficiency syndrome termed murine AIDS (MAIDS). Many of the features of the LP-BM5-initiated disease are shared with HIV/AIDS. Our lab has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD40 on B cells by CD154 on CD4 T cells. Despite this strict requirement for CD154 expression, whether CD4 T cell receptor (TCR) occupancy is essential for the induction of MAIDS is unknown. To block TCR engagement, Tg mouse strains with monoclonal TCR of irrelevant peptide/MHC specificities, all on MAIDS-susceptible genetic backgrounds, were tested: the study of a panel of TCR Tg CD4 T cells controlled for the possibility of serendipitous crossreactive recognition of virus-associated or induced-self peptide, or superantigen, MHC complexes by a given TCR. The results argue that TCR engagement is not necessary for the induction of MAIDS.
Li
Wen
W
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Green
William R
WR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D015728:Receptors, HIV; D012190:Retroviridae / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology
D018398:Homeodomain Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015728:Receptors, HIV; C064658:RAG-1 protein; D023201:CD40 Ligand