ABROGATION OF THE IMMUNOSUPPRESSIVE EFFECT OF DONOR SPLEEN CELLS ON RENAL ALLOGRAFTS IN THE RAT BY IRRADIATION OR HEAT TREATMENT

Abstract

In the donor-recipient strain combination Lewis (RT1¹) to Dark Agouti (RT1^a), indefinite renal allograft survival (MST> 100 days) was induced by pretreating recipient animals i.v. with 10⁶ to 10⁸ viable spleen lymphocytes, seven days before transplantation. Pretreatment with 10⁴ or 10⁵ cells was ineffective (MST 10 days). However when 10⁷ live, but heat-treated (55°C for 10 min) or irradiated (1000 rads) cells were sued, all the animals rejected the allograft in a normal fashion (MST 10 and 11 days, respectively). Median survival time of third-party controls was 10 days.

The relative amount of cell surface major histocompatibility anitgens (class I and class II) expressed by the three spleen cell preparations was investigted using monoclona antibodies and fluorescence activated cell sorter analysis and found to be similar. After 24 hr in culture, only 1% of heat-treated and 10% of irradiated cells were viable, in contrast to 75% of untreatd splenocytes, Trafficking of these lymphocytes in recipient animals was investigated by ⁵¹chromium labeling of the cells: 30% of lymphocytes had localized in the liver within 3 hr with littel difference in localization in localization among the different cell preparations. But, although 20% of normal and irradiated cells localized in the spleen within 3 hr, at no stage were more than 5% of the heat-treatd cells found in the spleen. It is suggested that the length of time viable donor lymphocytes remain in the recipient circulation is important in the induction of specific immunosuppression by spleen lymphocytes.