Down regulation of CD45 expression on CD4 T cells during acute renal allograft rejection: evidence of a decline in T suppressor/inducer activity.

Acute rejection is associated with the activation of helper and cytotoxic cells. A shifting balance between the suppressor/inducer CD45+ CD4+ and T helper/inducer (CD4+CD45-) cells may be responsible for the transition from quiescence to overt rejection. We examined the kinetics of CD45 expression on CD4+ T cells in renal allograft recipients from pretransplant values to acute rejection and after reversal of rejection, searching for a shift in balance between helper/inducer and suppressor/inducer cell subsets. Using two color flow cytometry, the peripheral blood levels of CD4+, CD4+CD45- [T helper/inducer (Thi)], CD4+CD45+ [T suppressor/inducer (Tsi)], CD3+, and CD8+ T cells subsets and their interrelationships, were determined in 49 patients prior to transplantation, and in 10 of them, during acute rejection and after its reversal. Results were analyzed and compared to data obtained from 10 healthy blood donors. Acute rejection was associated with a significant decline in CD45+ CD4+ expression compared to quiescent phase (22% +/- 3.7% vs. 26.5% +/- 3.2%, p = 0.05) and controls (29.5% +/- 6.2%, p = 0.01). No difference was observed compared to pretransplant levels (19.9% +/- 3.2%, p = ns). CD45-/CD45+ (Thi/Tsi) ratio was lowest during quiescence (0.75) compared to rejection (0.97, p = 0.05), in controls (0.98, p = 0.05) and pretransplant values (1.4, p = 0.01). Acute rejection was characterized by higher Thi/CD8+ and lower Tsi/CD8+ ratio (103 and 88 respectively, p = 0.045), compared to clinical quiescence (104 and 116 respectively, p = 0.039). These data suggest that acute rejection is associated with down regulation of CD4+CD45+ suppressor/inducer subset. This shift may account for the transition from quiescence to overt rejection, concurring with reports on CD4+CD45 regulatory function.