Cytotoxic pathways in the skin allograft rejection by CD4+ T cells
A Ito, M Minagawa, K Tomiyama, M Ito, K Kawai - Transplantation, 1999 - journals.lww.com
A Ito, M Minagawa, K Tomiyama, M Ito, K Kawai
Transplantation, 1999•journals.lww.comBackground. Two major mechanisms of T cell-mediated cytotoxicity are known: perforin-
dependent and Fas-dependent cytotoxic pathways. Previous studies in vitro demonstrated
that CD4+ cytotoxic T lymphocytes use the Fas pathway as a primary cytotoxic mechanism,
but the cytotoxic mechanisms used by CD4+ T cells in vivo are unclear. Methods. We
examined the cytotoxic pathways of CD4+ T cells in vivo using a skin allograft model, in
which athymic nu/nu mice were transplanted with skin allografts and reconstituted with …
dependent and Fas-dependent cytotoxic pathways. Previous studies in vitro demonstrated
that CD4+ cytotoxic T lymphocytes use the Fas pathway as a primary cytotoxic mechanism,
but the cytotoxic mechanisms used by CD4+ T cells in vivo are unclear. Methods. We
examined the cytotoxic pathways of CD4+ T cells in vivo using a skin allograft model, in
which athymic nu/nu mice were transplanted with skin allografts and reconstituted with …
Abstract
Background.
Two major mechanisms of T cell-mediated cytotoxicity are known: perforin-dependent and Fas-dependent cytotoxic pathways. Previous studies in vitro demonstrated that CD4+ cytotoxic T lymphocytes use the Fas pathway as a primary cytotoxic mechanism, but the cytotoxic mechanisms used by CD4+ T cells in vivo are unclear.
Methods.
We examined the cytotoxic pathways of CD4+ T cells in vivo using a skin allograft model, in which athymic nu/nu mice were transplanted with skin allografts and reconstituted with purified CD4+ T cells. Fas-deficient and perforin-deficient mice and anti-tumor necrosis factor (TNF)-α monoclonal antibody were used for inactivating each cytotoxic pathway in vivo.
Results.
The skin allografts from Fas-deficient mice were readily rejected by the athymic mice reconstituted with purified CD4+ T cells. Perforin-deficient CD4+ T cells could also reject Fas-deficient skin allografts. Furthermore, in vivo treatment with anti-TNF-α monoclonal antibody did not prevent the allograft rejection by CD4+ T cells in the absence of both Fas and perforin pathways.
Conclusions.
These results indicate participation of undefined mechanisms other than Fas, perforin, and TNF-α pathways in CD4+ T cell-mediated cytotoxicity in vivo.
Lippincott Williams & Wilkins