Purified human T cells stimulated with cross-linked anti-CD3 monoclonal antibody OKT3: rIL-1 is a co-stimulatory factor for CD4+CD29+CD45RA- T cells.
Accessory cells (AC) are believed to play two major roles in T-cell activation: they cross-link certain stimuli such as monoclonal antibodies, and they provide needed cytokines. To differentiate between these roles, we cross-linked OKT3 on highly purified T cells by means of Fc-specific goat anti-mouse IgG-coated polystyrene beads and studied T-cell activation after exogenously added cytokines. Following addition of AC, rIL-2, or rIL-1, CD25 was up-regulated, and the cells proliferated and became cytotoxic. Both CD4+ and CD8+ cells were activated in the presence of AC or rIL-2. In contrast, only CD4+CD29+CD45RA- cells responded in the presence of rIL-1. Anti-IL-2R p55 (anti-TAC) monoclonal antibody inhibited the proliferative response supported by rIL-2 or rIL-1. To inhibit proliferation of cells stimulated in the presence of AC, anti-TAC needed to be supplemented with anti-IL-6 antibodies, or to be added in a 10-fold higher concentration. Cultures with AC produced larger amounts of IL-2 than those supplemented with rIL-1. Only AC-containing cultures also produced detectable amounts of IL-6. These findings combined with the observation that none of 2000 purified T cells counted in each of six independent experiments expressed MHC class II antigens strongly suggest that rIL-1 can activate T cells directly, rather than indirectly by potentiating the function of contaminating AC.
Department of Laboratory Medicine/Pathology, University of Minnesota, Minneapolis 55455.
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S
Panzer
R L
RL
Geller
F H
FH
Bach
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D015704:CD4 Antigens / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D019012:Integrin beta1; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D006649:Histocompatibility Antigens; D019012:Integrin beta1; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens