CD8-CELLS RESPONDING TO RESIDUAL CLASS-I ANTIGENS, WITH HELP FROM CD4(+) CELLS STIMULATED INDIRECTLY, CAUSE REJECTION OF MAJOR HISTOCOMPATIBILITY COMPLEX-DEFICIENT SKIN-GRAFTS( EFFECTOR)

Background. Skin grafts from mice that are deficient in the expression of both class I and class II major histocompatibility complex (MHC) a ntigens are rejected rapidly by normal recipients. Methods. To determi ne the mechanism of this rejection, MHC-deficient skin grafts were pla ced on recipients with different degrees of antigenic disparity and on recipients depleted of selected T cell subpopulations, In addition, t he recipient's T cells were examined in vitro for their responses befo re and after graft rejection. Results. The results indicate that (1) C D4(+) cells provide help for this rejection by recognizing donor antig ens presented by recipient class II antigens, and (2) CD8(+) cells can participate as effector cells, recognizing residual class I antigens expressed by the MHC-deficient grafts. Conclusions. The primary conclu sion from these studies is that the supposedly MHC-deficient mice actu ally do have sufficient class I antigen expression to cause skin graft rejection, This finding prevents the use of these mice to answer defi nitively the question of whether grafts entirely lacking MHC antigens would be rejected, However, these studies do illustrate two important (although previously recognized) features of allogeneic skin graft rej ection: (1) that rejection can be initiated by help provided entirely through the indirect pathway, and (2) that help provided through the i ndirect pathway is available for effector T cells sensitized directly by donor cells, However, the results from these and other studies sugg est that indirect effector mechanisms would probably be able to destro y truly MHC-deficient grafts under some circumstances.