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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunologic enhancement of renal allografts from (Lewis times Brown Norway) F1 to Lewis rats was achieved by administering a single dose of antidonor serum at the time of transplantation. A series of grafts functioning for 1 to 4 months after transplantation were examined by light and immunofluorescence microscopy to evaluate the long-term protective effects of the enhancing serum and to determine if previously unobserved lesions appeared in long survivors. Despite the absence of detectable circulating cytotoxic alloantibody, long-term allografts showed necrotizing glomerular and arterial lesions which resembled those seen in acutely rejecting grafts and were compatible with humoral rejection. Thus, in this model, there is a late decline in the ability of passive enhancement to inhibit humoral rejection. Long-term grafts also developed tubular lesions with deposition of immunoglobulin and complement on the tubular basement membranes (TBM). Anti-TBM antibodies were demonstrated in recipients' sera and found to be organ specific but not major histocompatibility antigen or species specific. This tubular lesion is therefore a unique form of allograft injury in which the immune response is directed against tissue antigen(s) which are distinct from the major histocompatibility antigens that induce rejection.
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PMID:Immunologic enhancement of rat renal allografts. III. Immunopathologic lesions and rejection in long-surviving passively enhanced grafts. 109 34

Systemic adoptive transfer was employed to assess the immunosuppressive efficacy of antigen-specific suppressor T (Ts) cells purified from recipients treated with 3M KCl-extracted donor histocompatibility antigen (Ag) and cyclosporine (CsA). Suppressor cells were obtained from Wistar-Furth (WFu, RT-1u) hosts treated with a single i.v. injection of 5 mg 3M KCl-extracted donor Buffalo (Buf, RT-1b) antigen combined with a three-day course of CsA, a group that displays prolonged renal allograft survival (MST 23.2 +/- 10.2 days) compared with animals treated with CsA alone (MST 12.2 +/- 2.4 days). These noncytolytic, OX-8 phenotype, 800-rad-resistant/1500-rad-sensitive, nylon-wool-nonadherent and cyclophosphamide-sensitive suppressor T cells (1 X 10(6)) were adoptively transferred ten days after transplantation into virgin, secondary syngeneic hosts-thereby prolonging Buf graft survival from 7.2 to 17.5 days. The suppressor effect was immunologically specific; adoptive transfer did not prolong the survival of third-party Brown-Norway (BN) grafts (MST 10.4 +/- 3.1 days) compared with the nontreated control group (MST 11.0 +/- 2.9 days). The potency of Ts cells purified from Ag-CsA-treated hosts to transfer unresponsiveness into normal secondary WFu hosts (MST 17.5 +/- 8.0 days) was stronger than that of Ts cells from hosts treated with CsA only (MST 10.6 +/- 2.6 days). Moreover, in vitro stimulation of monoclonal-antibody-purified Ts cells by irradiated donor Buf spleen cells potentiated the in vivo induced suppressor activity, leading to an MST of 38.1 +/- 32.6 days; indeed 3 of 12 animals (25%) displayed permanent unresponsiveness. Furthermore, Ts cells from Ag-CsA-treated hosts displayed a synergistic effect with a three-day course of CsA administration into the secondary hosts (MST 24.2 +/- 8.0 days) compared with animals only treated with CsA (MST 12.2 +/- 2.4 days, P less than 0.001). Moreover, the combination of the Ag-CsA regimen with Ts cells administered one day after transplantation caused even greater prolongation of graft survival (MST 34.2 +/- 14.2 days) compared with Ag-CsA-treated hosts (MST 23.2 +/- 10.2 days, P less than 0.025). Thus adoptively transferred antigen-specific suppressor T cells may be explored to intensify the specific immunosuppressive effect of the Ag-CsA regimen to achieve long-term unresponsiveness.
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PMID:The immunosuppressive action of suppressor cells from antigen-cyclosporine-treated hosts on renal allograft survival. 241 93

Suppressor T cells were identified in situ within renal allografts of hosts rendered unresponsive by perioperative administration of donor histocompatibility antigen, which was extracted from donor spleen cells with 3M KCl, combined with cyclosporine (Ag-CsA). Infiltrating cells harvested from Buffalo (BUF, RT1b) renal allografts ten days after transplantation into Wistar-Furth (WFu, RT1u) rats treated with a single i.v. injection of 5 mg 3M KCl-extracted donor antigen (Ag) combined with a three day course of CsA inhibited the mixed lymphocyte culture (MLC) reaction between normal responder WFu and irradiated BUF cells (79.3% suppression, P less than 0.001), but not third-party Brown-Norway (BN, RT1n) stimulator cells (-5.4% suppression, NS). The suppressor effect was not due to cytolysis: the infiltrating cells did not lyse 51Cr-labeled concanavalin A (Con-A) blastoid BUF cells, as did the infiltrating cells from nonimmunosuppressed recipient allografts undergoing rejection responses toward BUF (49% specific cytolysis, E/T = 25), but not third-party BN, target cells five days after transplantation. The suppressor cells were nonadherent to plastic dishes and sensitive to monoclonal antibodies (Mab) W3/13 HLK (pan-T cells: % suppressor -17.9) or cytotoxic/suppressor cells with Mab OX-8 (-5.0% suppression), but not W3/25 (helper; 48.6% suppression, P less than 0.025). Moreover, adoptive transfer of 10(6) infiltrating cells from Ag-CsA-treated recipient allografts into virgin WFu hosts prolonged primary BUF graft survival from 7.2 to 14.0 days (P less than 0.05), but not third-party BN grafts (treated MST = 11.9 +/- 3.9 days versus untreated MST = 11.0 +/- 2.9 days, NS). On the other hand, infiltrating cells from CsA-only-treated recipient allografts could not transfer this effect (MST = 7.7 +/- 0.5 days, P less than 0.01). Finally, retransplantation of the BUF allograft from the Ag-CsA treated rat to a syngeneic, virgin WFu host ten days after primary transplantation yielded prolonged survival with MST 11.4 +/- 2.3 versus control primary graft survival in untreated animals of 7.2 +/- 0.6 days (P less than 0.001). BUF allografts from treated WFu hosts retransplanted into third-party BN rats did not display prolonged graft survival (MST = 9.2 +/- 1.1 days) compared with primary BUF grafts in untreated BN recipients (MST = 9.2 +/- 2.0 days, NS). The presence of suppressor T cells both in the spleen and in situ in renal allografts following Ag-CsA treatment suggests that local mechanisms may augment systemic elements to control the generation of alloimmunity.
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PMID:Suppressor cell activity of cells infiltrating rat renal allografts prolonged by perioperative administration of extracted histocompatibility antigen and cyclosporine. 293 56

Antigen-specific suppressor T cells are induced by donor histocompatibility antigen extracted from spleen cells with 3M KCl combined with cyclosporine (Ag-CsA). A single i.v. injection of 5 mg 3M-KCl-extracted donor Buffalo (Buf, RT1b) antigen (Ag) combined with a three day course of CsA prolonged renal allograft survival in Wistar-Furth (WFu, RT1u) hosts to a greater extent (MST 26.5 days) than CsA alone (MST 11.8 days). Peripheral blood lymphocytes (PBL) or spleen cells harvested from Ag-CsA-treated recipients ten days after transplantation inhibited the mixed lymphocyte reaction (MLR) between normal responder WFu cells and irradiated Buf cells (55.6% and 64.4% suppression, respectively, P less than 0.025), but not third-party Brown-Norway (BN, RT1n) stimulator cells (13.6% and -18.3% suppression, respectively, NS). The suppressor effect was not mediated by cytolytic cells; there was neither primary nor secondary cytolytic activity against 51Cr-labeled Con-A blastoid Buf cells. The suppressor cells were neither adherent to plastic dishes nor to nylon-wool columns. PBL irradiated with 800 rads, but not 1500 rads, suppressed the MLR. A single injection of cyclophosphamide (CY, 25 mg/kg) seven days after transplantation abrogated the suppression induced by Ag-CsA treatment. Moreover, PBL from Ag-CsA recipients failed to suppress the MLR, if depleted either of all T cells by treatment with monoclonal antibody (Mab) W3/13 HLK (pan T cells; % suppression -15.8), or of cytotoxic/suppressor cells with Mab OX-8 (-19.3% suppression) together with rabbit antimouse immunoglobulin and complement. On the other hand, PBL treated with the Mab W3/25 (helper) showed suppressor cell activity (+56.4%, P less than 0.001) similar to untreated cells (62.4%, P less than 0.001). Moreover, adoptive transfer of suppressor T cells purified from pooled lymphocytes by rosetting using Mab significantly prolonged the survival of donor-specific, but not third-party, test grafts in naive secondary hosts. Thus, these studies demonstrated antigen-specific suppressor T cells mediate the long-term unresponsiveness induced by the Ag-CsA regimen.
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PMID:Nature of the suppressor cells mediating prolonged graft survival after administration of extracted histocompatibility antigen and cyclosporine. 315 79