TY - JOUR
T1 - CTLA-4 can function as a negative regulator of T cell activation
AU - Walunas, Theresa L.
AU - Lenschow, Deborah J.
AU - Bakker, Christina Y.
AU - Linsley, Peter S.
AU - Freeman, Gordon J.
AU - Green, Jonathan M.
AU - Thompson, Craig B.
AU - Bluestone, Jeffrey A.
N1 - Funding Information:
We wish to thank Dr. D. Loh (Washington University) for his generous contribution of the 2C TCR transgenic mouse line and Dr. J. Miller (University of Chicago) for thoughtful review of the manuscript. J. A. 8. is an American Cancer Society Faculty Scholar, T. L. W. is the recipient of a National Science Foundation Predoctoral Fellowship, D. J. L. is supported by the Molecular and Cellular Biology Training Grant GM07183-19. C. Y. 8. is supported by a Pew Charitable Trusts Undergraduate Research Fellowship. This work was supported by PO1 Al35294, CA40218, Al35225, and a grant from the Repligen Corporation Animal care, flow cytometry, and peptide synthesis has been supported by the Cancer Research Center, CA14599.
PY - 1994/8
Y1 - 1994/8
N2 - CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 MAbs Inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.
AB - CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 MAbs Inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.
UR - http://www.scopus.com/inward/record.url?scp=0028484545&partnerID=8YFLogxK
U2 - 10.1016/1074-7613(94)90071-X
DO - 10.1016/1074-7613(94)90071-X
M3 - Article
C2 - 7882171
AN - SCOPUS:0028484545
SN - 1074-7613
VL - 1
SP - 405
EP - 413
JO - Immunity
JF - Immunity
IS - 5
ER -