Treatment with either anti-CD4 or anti-CD8 monoclonal antibodies blocks alpha beta T cell-mediated rejection of intestinal allografts in mice

Background. Rejection is the major barrier preventing the more widespread application of intestinal transplantation as treatment for intestinal failure, For this study, a one-way host-versus-graft murine model was used to investigate the contribution of T cell subsets to the rejection of allogeneic intestinal allografts, Methods, Intestinal grafts consisting of the donor jejunum and ileum were procured from C57BL/6J (syngeneic group) and B6C3F1/J (C57BL/6 x C3H/HeJ, allogeneic group) mice, These grafts were then transplanted into (1) normal, (2) antibody-treated, or (3) genetically mutated C57BL/6 mice, Mice were killed at predetermined intervals and the grafts assessed for rejection by a blinded pathologist, Results, No syngeneic mice demonstrated any evidence of rejection, In contrast, the recipients of allografts experienced progressive rejection, Recipient mice treated with tacrolimus developed significantly less severe allograft rejection, None of the alpha beta T cell-deficient recipient mice (T cell receptor beta chain knockout mice) experienced allograft rejection with follow-up ranging from 8 to 28 days, However, mice deficient in gamma delta T cells (T cell receptor delta chain knockout mice) rejected intestinal allografts in a manner indistinguishable from normal recipients, In order to investigate the role of CD4(+) and CD8(+) T cells, recipient mice were treated 2 days before transplantation with depleting monoclonal antibodies specific for either CD4(+) cells or CD8(+) cells, Depletion of either population of cells significantly inhibited allograft rejection. Conclusions, These data demonstrate that rejection of intestinal allografts in the murine model was absolutely dependent on alpha beta but not gamma delta T cells, Furthermore, both CD4(+) and CD8(+) T cells were necessary for small bowel allograft rejection, Additional studies will be required to determine whether the effects of monoclonal antibody treatment were due solely to depletion of T cells or were mediated at least in part through an active process that altered the functional properties of the targeted T cell subset.