Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat-stable antigen.
The B cell activation antigen B7/BB1 has been shown to co-stimulate growth of human T cells by binding the T cell molecule CD28. In mice, the heat-stable antigen (HSA) has also been shown to act as a co-stimulator for T cell growth. In this study, we have evaluated the contributions of B7 and HSA to the co-stimulatory activity of antigen-presenting cells (APC). Mouse B7 provides co-stimulatory activity for murine CD4 T cells in anti-CD3-induced proliferation. Human CTLA4Ig, a chimeric molecule comprising the extracellular region of CTLA-4 fused to an immunoglobulin C gamma fragment, binds to murine B7. We, therefore, use human CTLA4Ig and the hamster anti-HSA monoclonal antibody 20C9 to analyze the relative contributions of B7 and HSA to the co-stimulatory activity of murine spleen APC. Our data reveal that both murine B7 and HSA are expressed by dendritic cells and by low-density spleen B cells. Either CTLA4Ig alone or anti-HSA alone inhibited CD4 T cell proliferation to anti-CD3 by > 90%, while CTLA4Ig and anti-HSA together were far more efficient in inhibiting clonal expansion of CD4 T cells. These results demonstrate that functionally defined co-stimulation involves at least B7 and HSA and suggest that signals delivered by B7 and HSA synergize in promoting T cell growth.
Liu
Y
Y
Section of Immunobiology, Yale University School of Medicine, New Haven.
Jones
B
B
Brady
W
W
Janeway
C A
CA
Linsley
P S
PS
Linley
P S
PS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D000954:Antigens, Surface / Q000235:genetics / Q000502:physiology*; D018122:B7-1 Antigen; D001483:Base Sequence; D051927:CD24 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins