In vivo and in vitro suppression of T-cell receptor alpha/beta CD4- CD8- T lymphocytes by cyclosporine A.
We treated a patient with a combined immunodeficiency and disease pathology resembling GvHD with cyclosporine. This disorder was characterized by exfoliative dermatitis, lymphadenopathy, and lymphocytosis of a novel T-cell phenotype (CD3+ TCR alpha/beta+ CD4- CD8-). The patient's peripheral blood T cells had elevated cytolytic activity and expressed increased levels of IL2R, HLA-DR, and CD45RO. Treatment with CsA resulted in marked clinical improvement, resolution of the lymphocytosis, and reduced cytolytic activity of peripheral blood T cells. T-cell HLA-DR and IL2R expression was reduced by cyclosporine, but CD45RO remained intact on virtually all circulating T cells. CsA also inhibited the cytolytic activity and cytokine production of in vitro cultured TCR alpha/beta+ CD4- CD8- cell lines. Our data suggest that alleviation of the patient's clinical symptoms resulted from cyclosporine-mediated suppression of proliferation, cytotoxicity, and inflammatory cytokine production of TCR alpha/beta+ CD4- CD8- T lymphocytes in vivo. The response of this patient to cyclosporine, which was similar to that seen in true GvHD, provides further evidence that these conditions share common pathogenetic pathways.
Department of Pediatrics, University of Texas Medical Branch, Galveston 77550.
E G
EG
Brooks
D P
DP
Wirt
G R
GR
Klimpel
S
S
Vaidya
R M
RM
Goldblum
D015704:CD4 Antigens / Q000097:blood*; D016827:CD8 Antigens / Q000097:blood*; D002460:Cell Line / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000188:drug therapy; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine