Immunological analysis of rat renal transplant recipients exhibiting long-term survival following treatment with 15-deoxyspergualin in the early postoperative phase.

BACKGROUND

We previously reported that short-term administration of 15-deoxyspergualin (DSG), 5 mg/kg/day on postoperative days 4 through 7, prolonged survival of rat renal allografts indefinitely. We now report the immunologic environment of DSG-treated recipients in the early postoperative phase.

METHODS

TO (RT1u) rat kidneys were transplanted into WKAH (RT1k) rats. Peripheral blood lymphocytes (PBL), splenocytes (SPC) and graft infiltrating lymphocytes (GIL) were harvested from rejecting (untreated) recipients on day 7 (group AR) and from DSG-treated recipients on days 7 (Group DSG7) and 14 (group DSG14). Flow cytometric analysis was done to determine characteristics of these cells. Mixed lymphocyte culture reactions (MLRs) were also studied to examine suppressive activities of sera, SPC, and GIL of each group by adding them to TO/WKAH MLRs.

RESULTS

In all groups, the proportions of CD8- and interleukin 2 receptor (IL-2R)-positive cells were higher for GIL than for either PBL or SPC. The CD4/CD8 ratio was lowest in GIL. Comparing groups DSG7 and DSG14, significant decreases in the proportion of CD8- and IL-2R-positive cells were found only in GIL. Sera of all groups nonspecifically suppressed MLRs, independent of DSG-administration. GIL of all groups also nonspecifically suppressed MLRs, while these suppressive activities were not observed with SPC. Suppressive activities of GIL remained unchanged in the first 2 postoperative weeks.

CONCLUSIONS

Differences in the immunologic environment were reflected primarily in GIL. DSG seemed to decrease CD8- and IL-2R-positive cells in allografts. In the presence of DSG, this model may feature a predominance of nonspecific suppressor T cells over cytotoxic T cells during the first 2 postoperative weeks.