Reduction of the in vitro cytotoxic lymphocyte response produced by in vivo exposure to semiallogeneic cells: recruitment or active suppression?

Twenty-four hours after intravenous injection of (C57BL/6 X DBA/2)F1 hygrid lymphoid cells into C57BL/6 mice, the in vitro cytotoxic lymphocyte (CL) response of the C57BL/6 spleen and LN cells against DBA/2 alloantigens can be greatly reduced. The reduction is specific for the foreign alloantigens injected; is reduced by irradiating the cells before injection; develops significantly within 10 min of injection, thereafter increasing with a time constant of about 2 hr; varies with the number and origin of cells injected; can be induced byseveral subpopulations of injected cells within one tissue; varies with the host organ tested (e.g., injection of 10(4) semiallogeneic LN cells can reduce hose LN response more than 100-fold and have no effect on host spleen); and (for the LN response) is largely reversed by treatment with anti-H-2 antibody plus complement specific for the injected cells. The reduction appears to be induced by grafted cells entering host lymphoid organs rather than, e.g., host cells being specifically recruited to go elsewhere. When cocultured with normal cells, lymphoid cells from mice injected as above do not reduce the in vitro CL response of the normal cells but do if left in vivo for 7 days before testing. If left 1 day in vivo, followed by 4 days culture in vitro with the same alloantigen, they strongly reduce the normal cell response. The reduction is increased by both the in vivo and in vitro exposure. The grafted cells, once in the host lymphoid tissue, appear to activate a host suppressor mechanism which develops in vitro and reduces the CL response.