T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid-induced programmed cell death.
The mechanisms by which glucocorticoids suppress immune responses have not yet been clearly defined. In steroid-sensitive pathological conditions, an increase in gamma delta T cells can occur in certain untreated systemic autoimmune disorders and seems to be a peristent feature in most cases of systemic lupus erythematosus (SLE). Our previously published data demonstrated that immunosuppressive therapy normalized this expanded SLE T cell subset in parallel with clinical remission of the symptoms. To establish how corticosteroid treatment determines the disappearance of peripheral blood gamma delta T lymphocytes, circulating alpha beta and gamma delta T lymphocytes from seven SLE subjects with active disease and seven healthy individuals were cultured in the presence or absence of 10(-7) M Dexamethasone (DEX). Cell suspensions were then analysed for DNA fragmentation, characteristic of apoptotic cell death, by a new cytofluorimetric method. Conventional agarose-gel electrophoresis on the same T cell populations was carried out for comparison. Regular follow-ups for 6 months revealed in vivo steroid treatment determined a dramatic fall in SLE blood gamma delta T cells, and in vitro experiments seem to indicate that DEX-triggered apoptotic signals are confined to the double negative (CD4-CD8-) gamma delta T cell subpopulation which disappears after in vivo immunosuppressive therapy. Clinical and pathological remission of some autoimmune diseases is often obtained by corticosteroids. Our results offer new insights on the mechanisms through these hormones exert their potent inhibitory activities on immune system cells postulated to play a role in the generation of autoimmune responses.
Spinozzi
F
F
Department of Internal Medicine, University of Perugia School of Medicine, Policlinico Monteluce, Italy.
Agea
E
E
Bistoni
O
O
Travetti
A
A
Migliorati
G
G
Moraca
R
R
Nicoletti
I
I
Riccardi
C
C
Paoletti
F P
FP
Vaccaro
R
R
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002648:Child; D004247:DNA / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000502:physiology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D003907:Dexamethasone; D004247:DNA