Mitogenic stimulation of T cells reveals differing contributions for B7-1 (CD80) and B7-2 (CD86) costimulation.
The requirement of accessory cells for concanavalin A (Con A) activation of T cells suggests delivery of a separate costimulatory signal. However, the costimulatory pathways involved have not been identified. These studies assess the role of CD28-B7-mediated costimulation during T-cell activation by Con A. The B7-1/B7-2 binding protein CTLA4-Ig inhibited the proliferative response of primary lymph node cells to either Con A or soluble anti-CD3 mAb. This suppression was dose dependent and could be reversed by CD28 cross-linking. CTLA4-Ig also completely suppressed induction of interleukin-2 (IL-2) mRNA by Con A. CTLA4-Ig-mediated suppression was not due to blockade of the Con A 'receptor(s)' or of the primary activation signal (as measured by the intracellular calcium response). Although both B7-1 and B7-2 were up-regulated following Con A activation, each played a different role in proliferation and cytokine production. Individually, anti-B7-2 Fab partially inhibited the Con A response whereas anti-B7-1 Fab had no effect. However, the combination of anti-B7-1 and anti-B7-2 Fab completely suppressed proliferation and IL-2 production. Therefore, while a part of the Con A response requires B7-2, the remainder of the response can utilize either B7-1 or B7-2. Together, these results demonstrate that Con A activation of T cells requires the delivery of a separate costimulatory signal that is mediated almost entirely by the B7 receptors.
Perrin
P J
PJ
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD, USA.
Davis
T A
TA
Smoot
D S
DS
Abe
R
R
June
C H
CH
Lee
K P
KP
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003208:Concanavalin A; D002118:Calcium