CD28- T lymphocytes. Antigenic and functional properties.
A subset of CD8+ alpha beta-TCR/CD3+ T lymphocytes in adult human peripheral blood lacks expression of CD28, a membrane receptor for the B7/BB1 B cell differentiation Ag that is involved in T cell activation. CD28-8+ T cells were not observed in the thymus and were present at only low frequency in cord blood, suggesting that these cells may represent a type of "memory" population. Consistent with this interpretation, CD28-8+ T cells were morphologically large, granular lymphocytes and expressed CD54 (intercellular adhesion molecule-1), CD58 (lymphocyte function-associated Ag-3 (LFA)), and high levels of CD11a (LFA-1), but did not express Ag associated with acute activation (e.g., HLA-DR, CD25, CD69). Freshly isolated CD28-8+ T lymphocytes mediated potent anti-CD3 redirected cytotoxicity against FcR-bearing targets, demonstrating that the CD3/TCR complex is functional and that these cells possess cytolytic activity. However, the anti-CD3-induced proliferative response of CD28-8+ T cells was substantially less than CD28+8+ T cells and this deficiency could not be overcome by addition of exogenous IL-2. A large panel of T cell clones were produced from the CD28+8+ and CD28-8+ T cell populations by single cell sorting using a flow cytometer. CD28 expression was stable on clones derived from CD28+8+ T lymphocytes, whereas CD28 expression was quite variable and apparently reexpressed on some clones generated from the CD28-8+ T cell population. As with the freshly isolated cells, CD28-8+ T cell clones were cytotoxic, but anergic to anti-CD3- induced proliferation and could not be costimulated using B7 or CD58 (LFA-3) murine L cell transfectants. These results indicate that CD28- and CD28+ T cells may play different roles in an immune response.
DNAX Research Institute of Molecular and Cellular Biology, Department of Immunology, Palo Alto, CA 94304.
M
M
Azuma
J H
JH
Phillips
L L
LL
Lanier
D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018106:CD28 Antigens; D017252:CD3 Complex / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D013755:Tetradecanoylphorbol Acetate