Generation of H-2 class II-reactive CD8+ cells in mice after class II-disparate skin graft rejection

Clinical trials and experimental studies have demonstrated that donor T cells can play a critical role in preventing allogeneic marrow graft rejection. Results of a previous study showed that donor T cells were most effective for preventing rejection when they recognize an alloantigen expressed by recipient T cells and can cause graft-versus- host disease (GVHD). The present study examined models where marrow graft rejection can be prevented by donor T cells that do not recognize host alloantigens and cannot cause GVHD. Donor T cells prevented rejection of major histocompatibility complex (MHC) class I and II- disparate F1 marrow in parental recipients prepared with > or = 800 cGy total body irradiation (TBI) but not in those prepared with < or = 750 cGy TBI. In recipients prepared with high TBI exposures, rejection was mediated entirely by host CD8 cells. With lower TBI exposures, rejection was mediated by host CD4 cells and CD8 cells. These observations suggested the hypothesis that donor T cells prevent rejection mediated by host effectors that recognize donor MHC class I alloantigens but do not prevent rejection mediated by host effectors that recognize donor class II alloantigens. Consistent with this hypothesis, further experiments showed that F1 donor T cells can prevent rejection of MHC class I-disparate marrow in irradiated parental recipients but have no detectable effect on rejection of MHC class II-disparate marrow. We propose that the expression of MHC class I molecules on donor T cells makes it possible for these cells to inactivate the host response against donor class I alloantigens through a veto mechanism, whereas the absence of MHC class II molecules on murine T cells explains why these cells cannot inactivate the host response against donor class II alloantigens. Finally, donor CD4 cells and CD8 cells were equivalently effective for preventing rejection of F1 marrow in parental recipients, suggesting that veto activity is not restricted solely to the CD8 subset of murine T cells. A veto mechanism could enable donor T cells to prevent allogeneic marrow graft rejection without causing GVHD.

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PROVOCATION OF SKIN GRAFT REJECTION ACROSS MURINE CLASS II DIFFERENCES BY NON-BONE-MARROW-DERIVED CELLS

Transplantation Journal ◽

10.1097/00007890-198404000-00016 ◽

1984 ◽

Vol 37 (4) ◽

pp. 393-395 ◽

Cited By ~ 4

Author(s):

P. MICHAEL Stuart ◽

BONNIE BECK-MAIER ◽

ROGER W. MELVOLD

Keyword(s):

Bone Marrow ◽

Skin Graft ◽

Graft Rejection ◽

Class Ii ◽

Bone Marrow Derived Cells

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Differential involvement of CD4+ cells in mediating skin graft rejection against different amounts of transgenic H-2K(b) antigen.

Journal of Experimental Medicine ◽

10.1084/jem.173.1.261 ◽

1991 ◽

Vol 173 (1) ◽

pp. 261-264 ◽

Cited By ~ 13

Author(s):

M Kawai ◽

Y Obata ◽

N Hamasima ◽

T Takahashi ◽

A Uenaka ◽

...

Keyword(s):

Transgenic Mice ◽

Skin Graft ◽

Graft Rejection ◽

Class I ◽

Prolonged Survival ◽

Cell Surface Expression ◽

Cd4 Cells ◽

Cd8 Cells ◽

Differential Involvement

Differential involvement of CD4+ cells in mediating class I-disparate skin graft rejection was investigated using quantitatively different Kb transgenic mice as donors under conditions in which CD8+ cells were blocked in vivo by administration of anti-CD8 monoclonal antibody (mAb). Tg.H-2Kb-1 and -2 are C3H transgenic mice with 14 and 4 copies, respectively, of the H-2Kb gene. Cell surface expression of Kb antigen and the Kb antigenicity of skin for eliciting graft rejection with homozygous and heterozygous transgenic mice were correlated with the copy number. In vivo administration of anti-Lyt-2.1 (CD8) mAb markedly prolonged survival of heterozygous and homozygous C3H Tg.H-2Kb-2 skin grafted onto C3H mice, but prolonged survival of heterozygous Tg.H-2Kb-1 skin grafts much less and did not prolong survival of homozygous Tg.H-2Kb-1 grafts. Administration of anti-L3T4 (CD4) mAb alone did not have any effect on skin graft rejection. Administration of anti-L3T4 (CD4) mAb with anti-Lyt-2.1 (CD8) mAb blocked rejection in all combinations. These findings indicate that a quantitative difference of class I antigen caused differential activation of CD4+ cells under conditions in which CD8+ cells were blocked.

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Prevention of allogeneic marrow graft rejection by donor T cells that do not recognize recipient alloantigens: potential role of a veto mechanism

Blood ◽

10.1182/blood.v88.3.962.962 ◽

1996 ◽

Vol 88 (3) ◽

pp. 962-969 ◽

Cited By ~ 50

Author(s):

PJ Martin

Keyword(s):

T Cells ◽

Mhc Class I ◽

Graft Rejection ◽

Class Ii ◽

Class I ◽

Marrow Graft ◽

Cd8 Cells ◽

Donor T Cells ◽

Veto Mechanism ◽

Allogeneic Marrow

Abstract Clinical trials and experimental studies have demonstrated that donor T cells can play a critical role in preventing allogeneic marrow graft rejection. Results of a previous study showed that donor T cells were most effective for preventing rejection when they recognize an alloantigen expressed by recipient T cells and can cause graft-versus- host disease (GVHD). The present study examined models where marrow graft rejection can be prevented by donor T cells that do not recognize host alloantigens and cannot cause GVHD. Donor T cells prevented rejection of major histocompatibility complex (MHC) class I and II- disparate F1 marrow in parental recipients prepared with > or = 800 cGy total body irradiation (TBI) but not in those prepared with < or = 750 cGy TBI. In recipients prepared with high TBI exposures, rejection was mediated entirely by host CD8 cells. With lower TBI exposures, rejection was mediated by host CD4 cells and CD8 cells. These observations suggested the hypothesis that donor T cells prevent rejection mediated by host effectors that recognize donor MHC class I alloantigens but do not prevent rejection mediated by host effectors that recognize donor class II alloantigens. Consistent with this hypothesis, further experiments showed that F1 donor T cells can prevent rejection of MHC class I-disparate marrow in irradiated parental recipients but have no detectable effect on rejection of MHC class II-disparate marrow. We propose that the expression of MHC class I molecules on donor T cells makes it possible for these cells to inactivate the host response against donor class I alloantigens through a veto mechanism, whereas the absence of MHC class II molecules on murine T cells explains why these cells cannot inactivate the host response against donor class II alloantigens. Finally, donor CD4 cells and CD8 cells were equivalently effective for preventing rejection of F1 marrow in parental recipients, suggesting that veto activity is not restricted solely to the CD8 subset of murine T cells. A veto mechanism could enable donor T cells to prevent allogeneic marrow graft rejection without causing GVHD.

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