IMMUNOREGULATORY ACTIVITY IN ADULT-RAT TESTICULAR INTERSTITIAL FLUID - RELATIONSHIP WITH INTRATESTICULAR CD8(+) LYMPHOCYTES FOLLOWING TREATMENT WITH ETHANE DIMETHANE SULFONATE AND TESTOSTERONE IMPLANTS

Regulation of T-cell traffic and function in the adult rat testis was assessed following treatment with the specific Leydig cell cytoxin, et hane dimethane sulfonate (EDS), and s.c. testosterone implants to prev ent Leydig cell recovery. The distribution of T-cell subsets in the te stis was determined immunohistochemically using stereological techniqu es. Testicular T cell-inhibiting activity in the interstitial fluid wa s measured using a phytohemagglutinin-activated rat thymocyte prolifer ation bioassay. The mostly cytotoxic CD8(+) T-cell subset predominated over the CD4(+) (regulatory) T-cell subset in the normal rat testis. Destruction of the Leydig cells caused a rapid preferential increase i n testicular CD4(+) T cells, which was followed by an increase in both the CD8(+) subset and T cell-inhibiting activity in the Leydig cell-d eficient testis. After Leydig cell recovery, there was a significant s hift toward the CD8(+) T-cell subset in the EDS-treated testis but not in the EDS-treated/testosterone-implanted testis. Total T-cell number s and inhibitory activity in the testis returned to control levels reg ardless of whether the Leydig cells were allowed to recover. The level of inhibitory activity was closely related to the number of CD8(+) T cells in the testis across all experimental groups, but it showed no r elationship with pituitary hormones, macrophage numbers, or intratesti cular testosterone levels. The data suggest that 1) cytotoxic lymphocy tes have a potentially significant role in testicular function and 2) T cell-inhibiting activity in the testis interstitium is not substanti ally affected by changes in pituitary hormones or Leydig cell function , but appears to be related to local changes in immune activity.