Inhibition of IL-4 responses after T cell priming in the context of LFA-1 costimulation is not reversed by restimulation in the presence of CD28 costimulation.
Costimulation is one of several factors that influence the differentiation of CD4+ Th cell responses. Previously, we have shown that Ag presentation in the context of LFA-1 costimulation by fibroblasts transfected with class II and ICAM-1 (ProAd-ICAM) can drive naive CD4-positive T cells into cell cycle, but these T cells die by apoptosis 4-5 days after stimulation. In this report we show that the death of these cells can be prevented by the addition of exogenous IL-2 (20 U/ml) or by restimulation with Ag presented in the context of CD28 costimulation. Under these conditions, T cells go through extensive cell division and normal cell expansion. However, when T cells that have been primed by Ag presented in the context of LFA-1 costimulation are restimulated, they secrete IL-2 and IFN-gamma, but little or no IL-4. The inability of ProAd-ICAM-primed T cells to produce IL-4 was restored by the addition of IL-4 to the priming culture. However, IL-4 responses were not restored by representation of Ag in the context of CD28 costimulation, even as early as 24 h after priming with Ag presented by ProAd-ICAM cells. These findings suggest that differential expression of B7-1 and ICAM-1 by APCs during the initiation of immune responses may alter the differentiation of Th populations.
Jenks
S A
SA
Department of Molecular Genetics and Cell Biology, Committee on Immunology, University of Chicago, IL 60637, USA.
Miller
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics; D018106:CD28 Antigens / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007117:Immunization, Secondary; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014162:Transfection / Q000276:immunology
D018122:B7-1 Antigen; D018106:CD28 Antigens; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4