Costimulation of human CD4+ T lymphocytes with B7 and lymphocyte function-associated antigen-3 results in distinct cell activation profiles.
This study describes the distinct roles of B7 and LFA-3 in the regulation of T cell responses. Activation of CD4+ T cells with Chinese hamster ovary (CHO)-DR4/B7 and CHO-DR4/LFA-3 cells that present the superantigen staphylococcal enterotoxin A resulted in significant T cell proliferation and substantial production of TNF and IFN-gamma. Strong IL-2 production was recorded in B7-costimulated, but not LFA-3-costimulated, cultures. The presence of B7 induced a more vigorous and prolonged proliferative T cell response compared with LFA-3 costimulation. In contrast, LFA-3 was more efficient than B7 in mediating cell adhesion of CD4+ T cells. Costimulation with the CHO-DR4/B7/LFA-3 triple transfectant resulted in enhanced cell adhesion, proliferation, and cytokine production compared with either DR4/B7 or DR4/LFA-3 alone. Optimal production of IL-2 by naive and memory CD4+ T cells was seen only when cells were costimulated with B7, whereas IFN-gamma production was induced in memory cells by both LFA-3 and B7. The Jurkat T cell line responded to CHO-DR4/B7/LFA-3 in a manner similar to peripheral blood CD4+ T cells. Reverse transcriptase-PCR analysis of Jurkat cells stimulated with staphylococcal enterotoxin E and the different CHO transfectants revealed that the cooperative effect of B7 and LFA-3 on IL-2 production was also seen at the mRNA level. The large amounts of IL-2 produced by B7 costimulation indicate a paracrine function of the B7/CD28 pathway, whereas the LFA-3/CD2 pathway provides strong adhesion and may facilitate autocrine T cell expansion. Combined expression of the B7 and LFA-3 molecules seems to provide an optimal Ag-presenting function that ensures strong adhesion and optimal signal transduction.
Parra
E
E
Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Sweden.
Wingren
A G
AG
Hedlund
G
G
Björklund
M
M
Sjögren
H O
HO
Kalland
T
T
Sansom
D
D
Dohlsten
M
M
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018968:CD58 Antigens; D016466:CHO Cells; D002448:Cell Adhesion / Q000276:immunology; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D018968:CD58 Antigens; D016207:Cytokines; D004768:Enterotoxins; D008562:Membrane Glycoproteins; C026066:enterotoxin A, Staphylococcal