Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.
We demonstrate that the murine B7 (mB7) protein is a potent costimulatory molecule for the activation of resting murine CD4+ T cells through the T-cell receptor (TCR)/CD3 complex. Stable mB7-transfected Chinese hamster ovary cells, but not vector-transfected controls, synergize with anti-CD3 monoclonal antibody and Con A-induced T-cell activation, resulting ultimately in proliferation. mB7 exerted its effect by inducing production of interleukin 2 and expression of the interleukin 2 receptor. Thus, mB7 costimulates T-cell activation through the TCR/CD3 complex by positively modulating the normal pathway of T-cell expansion. In contrast to the pronounced effect of mB7 on the activation of T cells through the TCR/CD3 complex, the mB7-transfected CHO cell line costimulated T-cell activation via the glycosylphosphatidylinositol-anchored proteins Thy-1 and Ly-6A.2 only inefficiently. Finally, the combination of a calcium ionophore and mB7 is not sufficient to cause T-cell proliferation, while the combination of a calcium ionophore and phorbol 12-myristate 13-acetate (PMA) stimulates T cells efficiently. The signals that mB7 and PMA provide for murine T lymphocyte activation are therefore not interchangeable, although both costimulate activation through the TCR/CD3 complex.
Department of Pathology, Harvard Medical School, Boston, MA 02115.
H
H
Reiser
G J
GJ
Freeman
Z
Z
Razi-Wolf
C D
CD
Gimmi
B
B
Benacerraf
L M
LM
Nadler
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000950:Antigens, Ly / Q000737:chemistry / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology*; D018122:B7-1 Antigen; D015152:Blotting, Northern; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016466:CHO Cells; D000001:Calcimycin / Q000494:pharmacology; D006224:Cricetinae; D006017:Glycolipids / Q000737:chemistry; D017261:Glycosylphosphatidylinositols; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D010716:Phosphatidylinositols / Q000737:chemistry; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018800:Thy-1 Antigens; D014162:Transfection; D015854:Up-Regulation
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D018122:B7-1 Antigen; D017252:CD3 Complex; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D007376:Interleukin-2; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D018800:Thy-1 Antigens; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate