Immunosuppressive antilymphocyte serum. III. Different subpopulations of T lymphocytes are influenced at different doses of antilymphocyte serum.

In these experiments, we have examined the effect of antilymphocyte serum (ALS) on T lymphocyte subpopulations in animals receiving nonimmunosuppressive, weakly immunosuppressive, and strongly immunosuppressive doses of different pools of ALS. Nonimmunosuppressive (inactive) sera were defined by their inability to prolong Fischer skin grafts on Lewis recipients. Weak immunosuppression was considered to have been achieved at doses of active ALS that induced prolonged survival of Fischer skin homografts but not the more strongly antigenic Wistar-Furth homografts. Similarly, strong immunosuppression was induced with doses of active ALS that resulted in prolonged survival of not only Fischer but also the Wistar-Furth grafts. Examination of Lewis rats treated under these conditions indicated that weakly immunosuppressive ALS created a shift in peripheral T lymphocyte subpopulations with an increase in the absolute numbers of one subpopulation (lymphocytes capable of forming rosettes with guinea pig red blood cells in fetal calf serum). This population shift induced by active ALS was dose dependent and occurred in spleen slightly before lymph nodes. Nonimmunosuppressive antisera failed to induce this change. Moreover, although these doses of ALS were capable of prolonging the survival of Fischer skin grafts and inducing the population change, there was no loss of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) in vitro. However, at doses of antiserum capable of prolonging the survival of Wistar-Furth skin grafts, the in vitro reactivity of T lymphocytes to these mitogens was more consistently suppressed. These data suggested that the degree of immunosuppression achieved with different pools or doses of ALS was attributable to variation in the susceptibility of different T lymphocyte subpopulations to suppression by ALS.