Alloantigen specific TCR transgenic CD8~+T cells require IL-2 to mediate allograft rejection
- VernacularTitle:移植抗原特异性转基因CD8~+T细胞对白细胞介素2的依赖性
- Author:
Xuemin XU
;
Xiang XIAO
;
Xianchang LI
- Publication Type:Journal Article
- Keywords:
Interleukin-2;
CD8-positive T-lymphocytes;
Transgenes
- From:
Chinese Journal of Organ Transplantation
1996;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the role of IL-2 in regulating allograft rejection mediated by alloantigen-specific CD8~+ T cell.Methods T cell proliferation in vivo at a single cell level was examined using the CFSE dilution assay. IL-2 expression by activated CD4~+ versus CD8~+ T cells was determined by intracellular cytokine staining. The ability of alloantigen-specific CD8~+T cells in mediating allograft rejection was studied using the islet transplantation model.Results CD8~+ T cells divided vigorously in vivo in the allogeneic hosts regardless the presence or absence of CD4~+ T cells. CD4~+ T cells, but not CD8~+ T cells, were the primary source of IL-2 when both subsets were present. However, CD8~+ T cells could express high levels of IL-2 in the complete absence of CD4~+ T cells. In 2C TCR transgenic (Tg) mice in which the 2C TCR transgene was selectively expressed on the CD8~+ T cells that specifically recognized alloantigen (Ld) of Balb/c origin, islet allografts from Balb/c mice was promptly rejected by the 2CTg recipients with mean survival time of only 8 days. In contrast, in 2CTg mice with a genetic deletion of the IL-2 gene (2CTg-IL-2KO mice), the alloantigen specific CD8~+ T cells failed to mediate the islet allograft rejection and all the Balb/c islets survived for more than 50 days.Conclusions CD8~+ T cells appear to be very plastic in producing and utilizing IL-2. In the presence or absence of CD4~+ T cells, CD8~+ T cells can use CD4~+ derived or self derived IL-2 for proliferation and effector function respectively. In an alloantigen specific TCR transgenic model, the effector function of CD8~+ T cells is strictly IL-2 dependent. Thus, in situations where graft rejection is mediated solely by the CD8~+T cells, blocking IL-2/IL-2R pathway may be critically important in preventing transplant rejection.
