CD4+ T cells prevent skin autoimmunity during chronic autologous graft-versus-host-disease.
CD4 regulatory cells have been postulated to prevent autologous graft-vs.-host disease (GVHD). In order to test this hypothesis, we used BALB/c mice, a strain known to be resistant to autologous GVHD, which had received autologous stem cell transplantation (ASCT) and cyclosporine A (CsA). As expected, ASCT/CsA-treated BALB/c mice did not develop any sign of acute or chronic GVHD. However, depletion of CD4 T cells induced a skin disease with clinical and histological features of alopecia areata (AA), a CD8 T-cell-mediated human autoimmune skin disease. The hair loss in mice developing AA was associated with the infiltration of the skin by activated CD8 T cells. Analysis of the T-cell recovery in ASCT- and ASCT/CsA-treated mice showed that CsA induced an increase in the number of CD4+ 25+ T cells, suggesting that the lack of GVHD in ASCT/CsA treated-mice could be related to the expansion of this CD4 T-cell subset. Collectively these data show that CD4 T cells comprise regulatory cells controlling the onset of autologous GVHD and suggest that the naturally occurring CD4+ 25+ subset may be responsible for this effect.
Hequet
Olivier
O
INSERM U503, CH Lyon-Sud, HCL, Pierre Bénite, France. ohequet@club-internet.fr
Vocanson
Marc
M
Saint-Mézard
Pierre
P
Kaiserlian
Dominique
D
Nicolas
Jean François
JF
Bérard
Frédéric
F
D000505:Alopecia / Q000209:etiology; D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016827:CD8 Antigens / Q000378:metabolism; D002908:Chronic Disease / Q000628:therapy; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D036102:Peripheral Blood Stem Cell Transplantation; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014182:Transplantation, Autologous
D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine