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-a ssociated T lymphocytes, the mechanism responsible for the activation of these cells is unknown. To address this question, resting gamma del ta TCR+, CD3+, CD4-, CD8- cells isolated from the blood of healthy vol unteers were cultured with allogeneic dendritic cells (DC) or monocyte s, and their proliferative response measured. DC alone induced gamma d elta 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 cell s. 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+ ce lls from the gamma delta T cell population nearly abrogated the respon se to DC. These results demonstrate that resting gamma delta T cells r ecognize and respond to MHC class II determinants on allogeneic DC in a manner that is highly dependent on the CD28 activation pathway as we ll as molecules such as CD2 and CD11a that mediate cell-to-cell adhesi on.