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S M Stepkowski

Publications and source records attributed to S M Stepkowski.

At least 109 records · Page 6Linked to original sources
PubMed1987

Induction of transplantation tolerance in rats by spleen allografts. II. Evidence that W3/25+ T suppressor/inducer and OX8+ T suppressor/effector cells are required to mediate specific unresponsiveness.

The results presented in this report demonstrate that T cells, isolated from AGUS rats bearing long-term (WAG X AGUS)F1 spleen allografts adoptively transferred to irradiated AGUS recipients could not mediate the rejection of WAG hearts but rejected PVG. A hearts in acute fashion. Further, unresponsive T cells were able to suppress the capacity of adoptively transferred (40 X 10(6) normal T cells to reject WAG but not PVG.A heart allografts. We also studied the role of W3/25+ and OX8+ T cells subsets in the maintenance of unresponsiveness. Isolated W3/25+ or OX8+ unresponsive T cells were not able to mediate acute rejection, but were less effective in prolonging WAG allograft survival than the unresponsive whole T cell population, suggesting that both W3/25+ Ts1 and OX8+ Ts2 subsets were required for effective suppression in vivo. When, however, unresponsive W3/25+ T cells were infused simultaneously with normal OX8+ T cells, they could produce indefinite survival of WAG heart allografts. These results indicate that the unresponsive state induced by (WAG X AGUS)F1 spleen allografts transplanted to AGUS rats is maintained by the interaction of W3/25+ T suppressor/inducer and OX8+ T suppressor/effector cells.

Animals↗
PubMed1987

Induction of transplantation tolerance in rats by spleen allografts. III. The role of T suppressor cells in the induction of specific unresponsiveness.

Heterotopic (WAG x AGUS)F1 spleen allografts survive indefinitely when transplanted to normal AGUS recipients and induce long-term donor-specific unresponsiveness. In this report, we have examined the immune reactivity of spleen graft recipients soon after transplantation, in an attempt to define the immunological mechanisms responsible for the induction of donor-specific unresponsiveness. Unresponsiveness develops as early as one week after splenic transplantation. T cells obtained from the recipient lymph node and spleen exhibit reduced mixed lymphocyte reaction responses to donor (WAG) but respond normally to third-party (PVG) stimulators. In contrast, T cells obtained from the spleen graft are unresponsive to both donor and third-party stimulators. Donor specific T suppressor cells (Ts) appear in the recipient's lymph node and spleen by one week posttransplantation--however, at this time antigen nonspecific suppressor cells predominate in the spleen graft. Only minimal cytotoxic T cell activity could be detected in the spleen graft, with the host spleen and lymph nodes being devoid of cytotoxic T lymphocytes. Sera obtained one or two weeks following splenic transplantation did not contain cytotoxic alloantibodies, and only a very weak response could be detected at one month. These data demonstrate that the unresponsiveness associated with the spontaneous acceptance of spleen allografts is correlated with the early induction of antigen specific Ts in recipient lymphoid tissue and the presence of nonspecific suppressor cells at the graft site.

Animals↗
PubMed1987

The role of class I and class II MHC antigens in the rejection of vascularized heart allografts in mice.

We have examined the role of entire major histocompatibility complex (MHC) disparity, individual class II or class I alloantigens in the rejection of vascularized heart allografts. Our results demonstrate that entire MHC, as well as both class II and class I disparities, may induce acute heart graft rejection or severe and irreversible heart muscle destruction. However, in 1 of 2 combinations differing at class II and 1 of 5 differing at class I, hearts have shown a good function greater than 100 days postgrafting. Furthermore, each donor-recipient combination has demonstrated a unique pattern of heart allograft function as well as a degree of heart muscle damage. In conclusion, these data suggest that the rejection process depends upon multiple factors such as the immune-response-gene-regulated immunoresponsiveness of the recipient as well as the expression of alloantigens on heart grafts during the induction and effector phases of the immune response.

Animals↗
PubMed1987

Protein synthesis in heterotopically transplanted rat hearts.

This study examines protein synthesis in heterotopically transplanted rat hearts and several tissues of recipient rats. Donor hearts and recipient tissues synthesized many of the normally occurring proteins observed in tissues of unstressed rats. In addition, a stress-induced protein with a molecular mass of 71 kilodaltons was synthesized in donor heart, recipient heart and lung. Donor hearts incorporated more L-[35S]-methionine than did recipient hearts. Tissues of recipient rats also incorporated more label than the respective tissues of sham-recipient rats. These results suggest that ischemia, endured by the donor hearts during transplantation, induced these changes in protein synthesis.

Animals↗
PubMed1986

Induction of transplantation tolerance in rats by spleen allografts. I. Evidence that rats tolerant of spleen allografts contain two phenotypically distinct T suppressor cells.

We have examined suppressor cell activity in transplantation tolerant (TT) rats bearing vascularized spleen allografts in several different donor-recipient combinations. More than 60% of WAG (RT-1u) and 65% of AGUS (RT-1l) spleen allografts were permanently accepted when transplanted to AGUS and PVG (RT-1c) rats, respectively. All (WAG X AGUS)F1 to AGUS and (AGUS X PVG)F1 to PVG spleen allografts survived indefinitely. Unseparated LNC, TDL, and whole T cell or W3/25+, OX8- T cell populations obtained from AGUS rats bearing (WAG X AGUS)F1 spleens exhibited reduced mixed lymphocyte reaction (MLR) responses to the spleen donor, and to some extent to BN(RT1n) third-party stimulators, but responded normally to PVG.A(RT1a) stimulators. Coculture experiments demonstrated that lymph node cells (LNC) and thoracic duct lymphocytes (TDL) of TT rats contain RT1 specific suppressor cells. Furthermore, T cells isolated from all donor-recipient combinations contained two phenotypically distinct suppressor cell populations: a radiosensitive W3/25+, OX8- (Th/i) and a relatively radioresistant W3/25-, OX8+ (Ts/c). These Ts may be responsible for the maintenance of TT.

Animals↗
PubMed1986

The role of TDTH and Tc populations in organ graft rejection. I. Functional analysis of graft-infiltrating T cells.

To analyze the role of T cell subpopulations in the rejection of organ allografts, we developed a new model for obtaining large numbers of graft infiltrating cells (GICs). We isolated W3/25+ Th/DTH and OX8+ Ts/c from vascularized, irradiated rat spleen allografts. W3/25+ GICs obtained from spleen allografts transplanted to normal recipients were highly effective in eliciting cardiac allograft rejection when transferred to sublethally irradiated recipients, however, the OX8+ subset was incapable of eliciting rejection. On the other hand, when OX8+ GICs were obtained from spleen allografts transplanted to previously immunized recipients, they were as efficient as the W3/25+ Th/DTH subset in eliciting cardiac allograft destruction. These results indicate that the W3/25+, OX8- T cell is required for the rejection of primary organ allografts, but that the rejection of a secondary allograft by an immune recipient may be mediated, independently, by both W3/25+ and OX8+ cells.

Animals↗
PubMed1984

Suppressor cells in the thoracic duct lymph of tolerant, spleen-grafted rats.

Vascularized spleen allografts between two different inbred rat strains induce specific transplantation tolerance in vivo. Thoracic duct lymphocytes isolated from tolerant rats exhibited notable nonresponsiveness to donor stimulator cells in the mixed lymphocyte reaction. In-vitro co-culture experiments indicate that this nonresponsiveness reflects the activity of both specific and nonspecific suppressor cells. Since suppressor cells are present in tolerant animals, it is possible that the suppressor cells play an important role in maintaining spleen-induced transplantation tolerance.

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