T-LYMPHOCYTES BEARING THE GAMMA-DELTA T-CELL RECEPTOR ARE SUSCEPTIBLETO STEROID-INDUCED PROGRAMMED CELL-DEATH

The mechanisms by which glucocorticoids suppress immune responses have not yet been clearly defined. In steroid-sensitive pathological condi tions, an increase in gamma delta T cells can occur in certain untreat ed systemic autoimmune disorders and seems to be a persistent feature in most cases of systemic lupus erythematosus (SLE). Our previously pu blished data demonstrated that immunosuppressive therapy normalized th is expanded SLE T cell subset in parallel with clinical remission of t he symptoms. To establish how corticosteroid treatment determines the disappearance of peripheral blood gamma delta T lymphocytes, circulati ng alpha beta and gamma delta T lymphocytes from seven SLE subjects wi th active disease and seven healthy individuals were cultured in the p resence or absence of 10(-7) M Dexamethasone (DEX). Cell suspensions w ere then analysed for DNA fragmentation, characteristic of apoptotic c ell death, by a new cytofluorimetric method. Conventional agarose-gel electrophoresis on the same T cell populations was carried out for com parison. Regular follow-ups for 6 months revealed in vivo steroid trea tment determined a dramatic fall in SLE blood gamma delta T cells, and in vitro experiments seem to indicate that DEX-triggered apoptotic si gnals are confined to the double negative (CD4(-)CD8(-)) gamma delta T cell subpopulation which disappears after in vivo immunosuppressive t herapy. Clinical and pathological remission of some autoimmune disease s is often obtained by corticosteroids. Our results offer new insights on the mechanisms through these hormones exert their potent inhibitor y activities on immune system cells postulated to play a role in the g eneration of autoimmune responses.