CD4+ T cells, without CD8+ or B lymphocytes, can reject xenogeneic skin grafts

Abstract

Abstract: Previous experiments have shown that rejection of xenogeneic skin grafts by mice is particularly dependent on CD4+ T cells. There are two possible explantations for this finding: either 1) “help” provided by CD4+ T cells is essential for CD8+ T cell‐, B cell‐, or NK cell‐mediated effector mechanisms of rejection, or 2) CD4+ cells are themselves responsible for rejection, perhaps by some nonspecific effector mechanism. To examine these two hypotheses, we transplanted pig skin onto SCID mice and then reconstituted the mice with selected subpopulations of lymphocytes. Mice that did not received CD4+ T cells were unable to reject their xenografts, whereas those receiving CD4+ cells could do so in the absence of CD8+ cells or B cells and even when additionally depleted of NK cells by treatment with anti‐Asialo GM1 antibody. Additional experiments were performed both in vivo and vitro to confirm the absence in test mice of CD4+ or CD8+ and B lymphocytes, respectively. These results suggest that CD4+ T cells are not only necessary for rejection of xenogeneic skin grafts by mice, but that they can do so without CD8+ cells or B cells, and probably without NK cells. Since CD4+ cells in mice have been shown to recognize xenogeneic antigens indirectly, this suggests that a nonspecific effector mechanism may be involved in the rejection of xenografts. In these experiments allogeneic skin grafts behave quite differently as they could not be rejected by this mechanism.