Cellular and humoral immunity after allogeneic transplantation in the rat. IV. The effect of heterologous antilymphocyte serum on cellular and humoral immunity after allogeneic renal transplantation.

Abstract

Cellular and humoral immunity was measured in Lewis rats that received (Lewis X Brown Norway) F1 (L X BN) renal allografts with or without rabbit anti-Lewis lymphocyte serum (ALS). A 51Cr release assay and a microcytotoxicity assay were used to measure cellular immunity (CMI) of immune lymphoid cells at various times after transplantation. As measured by the 51Cr release assay, ALS markedly suppressed the development of CMI; this virtual absence of CMI correlated well with the lack of immunological damage to renal allografts as measured by low levels of blood urea nitrogen (BUN) and prolonged allograft survival. As measured by the microcytotoxicity assay, the development of CMI was slightly delayed by ALS and had no relationship to levels of BUN. Also, following transplantation and ALS treatment, serum antibody production was almost completely suppressed. The disparate courses of CMI, as measured by the 51Cr release and microcytotoxicity assays, may be attributable to measurement of different populations of effector cells in each or to the measurement of different states of cellular immune activity in vitro. The mechanism by which ALS causes indefinite renal allograft survival is not clear. As measured by the 51Cr release assay, ALS can inhibit the cytotoxic effect of immune lymphoid cells in vitro in the absence of complement. Rats given ALS at various times prior to renal transplantation gradually recovered the ability to develop CMI as the interval between ALS pretreatment and transplantation was lengthened. Significant recovery of the ability to develop CMI was evident by 50 days after ALS pretreatment, and full recovery had occurred by 100 days. In contrast, all allograft recipients given ALS at the time of transplantation survived more than 100 days with relatively normal levels of BUN. The mechanism by which ALS causes indefinite renal allograft survival may be suppression of CMI for sufficient time to allow production in vivo of blocking serum factors that inhibit CMI and prevent rejection. Immunological damage to the allograft is then determined by the continued suppression of CMI by the blocking serum factors.