Inhibition of IL-2 synthesis by donor-specific suppressor T cells in a renal transplant recipient.
A study was conducted to elucidate the mechanism of donor-specific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-specific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-specific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-specific suppressor T cells that produced a humoral non-specific suppressive factor only when stimulated by the donor PBL, and this factor suppressed MLR and CML by inhibiting IL-2 synthesis of the PBL.
Second Department of Surgery, Hiroshima University, School of Medicine, Hiroshima City, Japan.
T
T
Okimoto
H
H
Yahata
Y
Y
Fukuda
K
K
Hayamizu
K
K
Dohi
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005220:Fathers; D005260:Female; D006085:Graft Survival; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009035:Mothers; D016853:Muromonab-CD3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016853:Muromonab-CD3; D011994:Recombinant Proteins; D003165:Complement System Proteins