Transfusion of polarized TH2-like cell populations into SCID mouse cardiac allograft recipients results in acute allograft rejection

It has been hypothesized that TH1 cells mediate the archetypical cell-mediated immune response of acute allograft rejection, whereas TH2 cells promote allograft acceptance, To test this, we transfused SCID cardiac allograft recipients with polarized TH1-like or TH2-like graft-reactive T cells, and monitored graft function and graft-reactive immune responses in the graft recipients. Polarized TH1-like cells, which were generated in vitro by stimulating syngeneic splenocytes with donor alloantigens in the presence of anti-IL-4 mAb, produced IFNg but not IL-4 when restimulated with donor alloantigen. Polarized TH2-like populations, which are generated in vitro by stimulating syngeneic splenocytes with donor alloantigens in the presence of IL-4, produced IL-4 but not IFNg when restimulated with donor alloantigen, Interestingly, bioassays of culture SN from restimulated TH1 but not TH2 cells revealed IL-2 production, although LDA analyses revealed that the TH1 and TH2 cells had identical frequencies of IL-2-producing cells. Transfusion of TH1-like cells into SCID cardiac allograft recipients resulted in acute rejection within 7-10 days that was characterized by cellular infiltration, myocyte necrosis, and edema, Graft-infiltrating cells (GIG) recovered from TH1-transfused animals contained large numbers of graft-reactive IL-2-producing cells (68-269/10(6) GIC), but no LDA-detectable IL-4-producing cells. These data support the hypothesis that donor-reactive TH1 cells can promote acute allograft rejection, In contrast to the hypothesis, transfusion of the polarized TH2-like population into SCID cardiac allograft recipients also resulted in histologically similar acute rejection within 7-10 days, Infiltrating cells recovered from TH2-transfused allografts contained large numbers of graft-reactive (109-1458/10(6) GIC), LDA-detectable, IL-4-producing cells-indicating that the TH2 cells had arrived at the graft-but promoted acute allograft rejection rather than allograft acceptance.