TY - JOUR
T1 - CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation
AU - Krummel, Matthew F.
AU - Allison, James P.
PY - 1995/8/1
Y1 - 1995/8/1
N2 - The importance of the B7/CD28/CTLA-4 molecules has been established in studies of antigen-presenting cell derived B7 and its interaction with the T cell costimulatory molecule CD28. CTLA-4, a T cell surface glycoprotein that is related to CD28, can also interact with B7-1 and B7-2. However, less is known about the function of CTLA-4, which is expressed at highest levels after activation. We have generated an antibody to CTLA-4 to investigate the consequences of engagement of this molecule in a carefully defined system using highly purified T cells. We show here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4. Cross-linking of CTLA-4 together with the TCR and CD28 strongly inhibits proliferation and IL-2 secretion by T cells. Finally, results show that CD28 and CTLA-4 deliver opposing signals that appear to be integrated by the T cell in determining the response to activation. These data strongly suggest that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTLA-4.
AB - The importance of the B7/CD28/CTLA-4 molecules has been established in studies of antigen-presenting cell derived B7 and its interaction with the T cell costimulatory molecule CD28. CTLA-4, a T cell surface glycoprotein that is related to CD28, can also interact with B7-1 and B7-2. However, less is known about the function of CTLA-4, which is expressed at highest levels after activation. We have generated an antibody to CTLA-4 to investigate the consequences of engagement of this molecule in a carefully defined system using highly purified T cells. We show here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4. Cross-linking of CTLA-4 together with the TCR and CD28 strongly inhibits proliferation and IL-2 secretion by T cells. Finally, results show that CD28 and CTLA-4 deliver opposing signals that appear to be integrated by the T cell in determining the response to activation. These data strongly suggest that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTLA-4.
UR - http://www.scopus.com/inward/record.url?scp=0029120245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029120245&partnerID=8YFLogxK
U2 - 10.1084/jem.182.2.459
DO - 10.1084/jem.182.2.459
M3 - Article
C2 - 7543139
AN - SCOPUS:0029120245
SN - 0022-1007
VL - 182
SP - 459
EP - 465
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -