Changes in lymphocyte recirculation and liberation of the adoptive memory response from cellular regulation in irradiated recipients

Abstract

Thoracic duct lymphocytes from previously immunized (AS2 x AS)F1 rats ('TDL) were adoptively transferred to syngeneic recipients and triggered by soluble HSA (s-HSA) the following day. The response of 'TDL in an irradiated recipient was almost two orders of magnitude greater than the response in a nonirradiated adult host. The affinity of the antibody in the adult recipients was significantly reduced but increased with time. Nonirradiated young recipients (3 weeks old) also supported an adoptive memory response which was comparable in quantity and quality to that found in irradiated hosts. The response of 'TDL declined progressively when transferred into 2-week-old or 4-week-old radiation chimeras, or was reduced in irradiated hosts when the memory cells were mixed together with nonimmune TDL. The experiments indicate that the differential response between the adult and irradiated recipient is the result of a restrictive control in the former host rather than an enhancing factor in the latter. Lymphocytes in the nonimmune population regulate both the expansion and maturation of the adoptive memory response, the high energy-binding B cells being at a selective disadvantage. Host irradiation effectively liberates the adoptive response from this cellular control mechanism. A comparative study of transferred, [14C]leucine-labeled TDL showed that distribution and homing of lymphocytes to lymph nodes and spleen was not altered by irradiating the recipients. However, adoptively transferred cells almost completely failed to recirculate in irradiated rats, in contrast to normal recipients. But, the injection of large numbers of unlabeled TDL following irradiation forced more labeled cells into the recirculating pool, suggesting that saturation of depleted lymphoid tissue with lymphocytes is an important factor regulating lymphocyte traffic. The relevance of this "saturation effect" in regulating the adoptive memory response is discussed.