IMMUNE MECHANISMS IN ORGAN ALLOGRAFT REJECTION

Publisher Website
Google Scholar
Abstract
The role of T and B lymphocytes in rejection of cardiac allografts bearing isolated major histocompatibility complex (MHC) subregion RT1.B/D encoded class II Ia disparities was investigated using natural and congenic recombinant inbred rats (RP, PVG RT1r1). RT1.B/D-disparate heart grafts were shown in 3 strain combinations (RP .fwdarw. WF, WF .fwdarw. [RP .times. PVG RT1l] F1, and PVG RT1r1) to induce a brisk humoral response (complement-dependent cytotoxicity [CDC] titers > 26) with specificity for class II determinants as evidenced by strain and tissue distribution of susceptible targets. Cytotoxic T cells (Tc) generated in parallel effected equivalent lysis (in the 4-h 51Cr-release LMC [lymphocyte mediated cytotoxicity] assay) of con A [concanavalin A] and lipopolysaccharide (LPS) blasts of the same strains. Specificity of Tc for class II determinants was demonstrable by specific inhibition of killing (.simeq.50%) by anti-Ia antibody preparations (monoclonal OX4 and antiserum ATH anti-ATL) with specificity for class II products of MHC subregions RT1.B and RT1.D, respectively. Adoptive transfer studies revealed that antibody and cytotoxic effectors (W3/25+, OX8+) with specificity for class II Ia determinants, though potentially injurious, are not required for rejection of cardiac allografts transplanted across isolated RT1.B/D disparities (RP.simeq.WF) because transfer even of small numbers (0.5 .RTM. 106) of helper T cells (W3/25+, OX8-) responsible for adoptive transfer of delayed type hypersensitivity to alloantigen, effected rejection in the absence of detectable antibody or Tc. In the immune response to alloantigen both cytotoxic T cell generation and a humoral immune response develop in parallel with that other form of cellular immunity, akin to classic delayed or tuberculinlike hypersensitivity, itself potentially a potent effector mechanism in organ allograft rejection.

This publication has 20 references indexed in Scilit: