Cellular and molecular basis of human gamma delta T cell activation. Role of accessory molecules in alloactivation.
Although gamma delta T cell receptor-bearing lymphocytes (gamma delta T cells) constitute a significant minority of circulating and tissue-associated T lymphocytes, the mechanism responsible for the activation of these cells is unknown. To address this question, resting gamma delta TCR+, CD3+, CD4-, CD8- cells isolated from the blood of healthy volunteers were cultured with allogeneic dendritic cells (DC) or monocytes, and their proliferative response measured. DC alone induced gamma delta T cells to proliferate, with a peak response on the sixth day of culture. Pretreatment of DC with an anti-HLA-DR mAb, but not anti-HLA class I or anti-CD1 mAbs, inhibited the response of gamma delta T cells. Antibodies to gamma delta T cell receptor, CD2, CD3, or CD11a were also inhibitory, whereas antibodies to alpha beta T cell receptor, CD4, CD5, and CD8 had no effect. Although only 40-60% of freshly isolated gamma delta T cells expressed CD28, mAbs directed against CD28 or its ligand, CD80, were markedly inhibitory. Moreover, removal of CD28+ cells from the gamma delta T cell population nearly abrogated the response to DC. These results demonstrate that resting gamma delta T cells recognize and respond to MHC class II determinants on allogeneic DC in a manner that is highly dependent on the CD28 activation pathway as well as molecules such as CD2 and CD11a that mediate cell-to-cell adhesion.
Takamizawa
M
M
Department of Pathology, Stanford University School of Medicine, California 94305.
Fagnoni
F
F
Mehta-Damani
A
A
Rivas
A
A
Engleman
E G
EG
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta