Control of memory CD4 T cell activation: MHC class II molecules on APCs and CD4 ligation inhibit memory but not naive CD4 T cells.
Memory or antigen-experienced CD4 T cells differ from naive CD4 T cells both phenotypically by cell surface marker expression, and functionally by their dissimilar pattern of cytokine secretion and activation requirements through their T cell receptor (TCR). We show here that activation of memory CD4 T cells (CD45RBlo subset), but not naive CD4 T cells (CD45RBhi subset), is inhibited by MHC class II molecules on antigen-presenting cells and by CD4 ligation. We propose that the selective negative signal in memory cells is a direct result of the differences in signaling via CD4 and CD3, exemplified in the disparate pattern of tyrosine-phosphorylated proteins visible after activation of the two subsets. In vivo, this inhibitory signal may serve to prevent irrelevant interactions between memory CD4 T cells and bystander MHC class II+ cells, and may also be responsible for the defective functioning of memory CD4 T cells in AIDS.
Farber
D L
DL
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
Luqman
M
M
Acuto
O
O
Bottomly
K
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007739:L Cells; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019000:Phosphotyrosine; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017252:CD3 Complex; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens