Accessory signalling by B7-1 for T cell activation induced by anti-CD2: evidence for IL-2-independent CTL generation and CsA-resistant cytokine production.
Resting T cells can be activated by selected pairs of anti-CD2 MoAb. Activation is dependent on the presence of accessory cells, which can be replaced by either anti-CD28, or by the combination of IL-1 beta and IL-6. The present study was undertaken to investigate accessory signalling by B7-1, the natural ligand of CD28, in this pathway of T cell activation. 3T6 mouse fibroblasts were transfected with human B7-1 and used as accessory cells in cultures of purified resting human T cells. In the presence of a stimulating pair of anti-CD2 MoAb, T cell proliferation, production of cytokines (IL-2, IL-4, IL-10, GM-CSF, IFN-gamma and TNF-alpha), and generation of cytotoxic T lymphocytes were all supported by B7-1(+) 3T6 cells but not by control 3T6 cells. Blocking studies with anti-IL-2 + anti-IL-2R MoAb revealed both IL-2-dependent and IL-2-independent CTL generation after B7-1-mediated costimulation. Moreover, a partial or complete resistance to inhibition with CsA was observed for IL-2 production and CTL generation respectively in the presence of the costimulatory signal derived from B7-1-CD28 interaction. Anti-CD2 MoAb with B7-1 costimulation could directly induce proliferation, IL-2 production and generation of CTL activity in highly purified CD8+ T cells without the help of CD4+ T cells. We conclude that CD28 ligation with the natural ligand B7-1 provides a strong accessory signal for CD4 and CD8 cell activation through CD2.
Van Gool
S W
SW
Department of Pathophysiology, Catholic University of Leuven, Belgium.
Kasran
A
A
Wallays
G
G
de Boer
M
M
Ceuppens
J L
JL
D000328:Adult; D018122:B7-1 Antigen / Q000502:physiology*; D018801:CD2 Antigens / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D016572:Cyclosporine