Recruitment of unsensitized circulating lymphocytes to sites of allogeneic cellular interactions

The recruitment of indium-111-labeled unsensitized lymphocytes (ULs) from the circulation into healed subcutaneous urethane sponge implants inoculated with specifically sensitized T lymphocytes (SSLs) and allogeneic target cells was studied in mice. Intravenously injected ULs were preferentially recruited to the site of specific effector-target interaction. Preferential recruitment was demonstrable within 1 hr of i.v. injection and was maximal at 4 hr. The recruitment of ULs was proportional to the number of SSLs or targets injected into the sponge. Effector cells capable of mediating the recruitment of ULs when presented with the sensitizing alloantigenic cells are detectable early in mixed lymphocyte culture (MLC) prior to the development of strong cytotoxicity. Furthermore, effector cells can be generated in MLC between H-2 identical but Mls-disparate strains in which a proliferative response occurs, but few cytotoxic cells develop. Depletion of Lyt-2+ cells from day 5 MLC abrogates cytotoxicity, but the capacity of the remaining cells to mediate recruitment is not changed. In contrast, depletion of Lyt-1+ cells does not alter cytotoxicity, but significantly reduces recruitment mediated by the remaining sensitized cells. These results suggest that recruitment of circulating lymphocytes to the site of an allograft response is mediated by an immunologicaly specific interaction between SSLs and alloantigen. These SSLs may be proliferating noncytotoxic lymphocytes or cytotoxic T lymphocytes. The capacity of a specific immune interaction at the allograft site to recruit circulating lymphocytes may be a rapid and potentially important mechanism of immune amplification in allograft rejection.