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.
Brooks
E G
EG
Department of Pediatrics, University of Texas Medical Branch, Galveston 77550.
Wirt
D P
DP
Klimpel
G R
GR
Vaidya
S
S
Goldblum
R M
RM
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