ANALYSIS OF IMMUNOSUPPRESSION GENERATED BY GRAFT VERSUS HOST REACTION .2. CHARACTERIZATION OF SUPPRESSOR CELL AND ITS MECHANISM OF ACTION

Abstract

Spleen cells from (CBA .times. C57/BL) F1 mice undergoing graft-vs.-host (GVH) reaction induced by injection of parental cells 7-14 days previously are capable of suppressing an immune response by normal or primed F1 spleen cells to chicken erythrocytes and levan in vivo and sheep erythrocytes in vitro. The cells in these GVH spleens which were responsible for the suppression were sensitive to treatment with anti-.theta. serum, resistant to 900 rad irradiation in vivo and not retained by anti-immunoglobulin columns. Suppressor activity in vitro was present only in the non-adherent fraction of these GVH cell suspensions. The T[thymus-derived]-cell fraction purified by affinity chromatography, suppressed the in vitro response of macrophage-depleted normal F1 cells to DNP[dinitrophenol]-levan. Collectively, these observations imply that suppressor T cells generated by GVH reaction can affect B[bone marrow-derived]-cell functions directly without intermediary macrophage participation. Spleen cells from (CBA .times. C57/BL) F1 mice undergoing GVH reaction induced by C57/BL cells were depleted of their F1 content by treatment with anti-CBA alloantiserum. The suppressive activity of the residual donor component was still expressed against other F1 cells (AKR .times. C57/BL) which were H-2 [histocompatibility] compatible with the original host, but not against H-2-incompatible cells (DBA/1 .times. C57/BL) F1. The latter were suppressed in the presence of (CBA .times. C57/BL) F1 cells. Interaction of donor T cells with F1 target cells containing those H-2 antigens towards which they are sensitized is mandatory for the subsequent manifestation of immunosuppressive activity. GVH cells suppressed the response of primed F1 cells in double Marbrook chambers when the 2 populations were separated by a cell-impermeable membrane, provided the GVH suspension contained F1 cells to which donor T cells were sensitized. This suggests that soluble factors are involved in the mechanism of GVH-induced immunosuppression.