Migration patterns and functional activity of cloned cytotoxic T lymphocytes in syngeneic and allogeneic mice.

The quantitative distribution of cytolytic T lymphocytes (CTL) generated in mixed leukocyte culture (MLC) and an interleukin-2 (IL-2)-dependent, CTL clone (WRL-A3) was investigated in various tissues of irradiated syngeneic and allogeneic mice. In addition, the ability of the WRL-A3 CTL clone to remain viable and retain antigen specificity following in vivo passage was evaluated. Injection i.v. of 51Cr-labeled cultured CTL resulted in: (1) extensive deposition of cells in the lungs with significantly more lymphocytes being recovered in allogeneic as compared with syngeneic lung tissue; (2) minimal accumulation in spleen with more in syngeneic than in allogeneic tissue; and (3) no localization in blood, femurs, thymus, or lymph nodes. The migration rate of cultured CTL exiting the lung during the first 4 hr was markedly faster in syngeneic than in allogeneic recipients and was directly associated with the distribution of these cells in other tissues at 24 hr. The WRL-A3 CTL clone recovered from irradiated syngeneic and allogeneic lung tissue at 1, 3, 6, 8, and 13 days after i.v. injection remained viable, even though no exogenous IL-2 was administered to the recipient mice. The recovered cells proliferated when recultured with IL-2, and retained their antigen specificity for Qed-1b target cells after in vivo passage. These findings indicate that restricted and undesirable tissue distribution, rather than impaired viability or loss of antigenic specificity, is the major obstacle to successful use of cultured CTL for adoptive immunotherapy of disseminated cancer.