Functional consequences of costimulation by ICAM-1 on IL-2 gene expression and T cell activation.
LFA-1 is a well-recognized adhesion molecule, but its role in providing costimulatory signals to T cells has remained controversial. We have compared the ability of class II-positive transfectants that do and do not coexpress ICAM-1 (ProAd and ProAd-ICAM) to activate Ag-specific Th1 clones and naive CD4-positive T cells isolated from TCR transgenic mice. Ag presentation by ProAd to Th1 clones can induce calcium-dependent signaling events after engagement of the TCR, as evidenced by the nuclear localization of the transcription factors NF-AT and NF-kappaB. Nevertheless, coexpression of ICAM-1 or B7-1 on ProAd is required to induce detectable levels of IL-2 gene expression in either Th1 clones or naive T cells. In Th1 clones, activation by ProAd-ICAM induces very transient IL-2 mRNA expression that does not result in detectable IL-2 secretion or T cell proliferation. In naive T cells, the duration of IL-2 mRNA expression is longer, allowing for a transient burst of IL-2 protein that is sufficient to drive the cells into the cell cycle. In spite of this initial response, Ag presentation by ProAd-ICAM is a tolerogenic signal to naive T cells, and responding T cells undergo apoptosis 4 to 5 days poststimulation. These data suggest that engagement of LFA-1 can provide sufficient costimulatory signals to induce T cell activation and IL-2 gene expression, but cannot protect against anergy induction or provide for T cell survival.
Zuckerman
L A
LA
Committee on Immunology, Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637, USA.
Pullen
L
L
Miller
J
J
D000818:Animals; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000235:genetics*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1; D013936:Thymidine