CD28 delivers costimulatory signals for superantigen-induced activation of antigen-presenting cell-depleted human T lymphocytes.
The CD28 pathway functions to provide costimulatory signals that are required for TCR-mediated activation of T cells. The role of this pathway in superantigenic stimulation of resting human T cells was investigated in the presence and absence of APC using a streptococcal superantigen, pep M5. Anti-B7/BB1 mAb inhibited the response of T cells when pep M5 was presented by APC. In the absence of APC, cross-linking CD28 by anti-CD28 mAb provides signals that synergize with APC-derived cytokines and with superantigen resulting in T cell proliferation. Anti-HLA-DR, -DQ mAb blocked the response of T cells to pep M5 presented by APC but had no effect on the response of purified T cells to the superantigen costimulated via CD28 cross-linking. These data show that the CD28 pathway is important for superantigenic stimulation of T cells and that signaling through this pathway can substitute for the APC-associated costimulatory activity that is essential for T cell stimulation. Moreover, the results are consistent with the notion that, in the presence of appropriate costimulation, pep M5 can directly interact with T cells and induce them to proliferate.
Ohnishi
H
H
Veteran's Affairs Medical Center, Memphis, TN 38104.
Tanaka
T
T
Takahara
J
J
Kotb
M
M
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology; D018122:B7-1 Antigen; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D018106:CD28 Antigens; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D018106:CD28 Antigens; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; C014689:streptococcal M protein; D013755:Tetradecanoylphorbol Acetate