B A Bach

Mechanisms of regulation of cell-mediated immunity: anti-I-A alloantisera interfere with induction and expression of T-cell-mediated immunity to cell-bound antigen in vivo.

The ability to modulate immunity to cell-bound antigen with anti-I-A alloantisera has been assessed. It was found that anti-I-A antiserum could inhibit the generation of T cell-dependent delayed-type hypersensitivity (DTH) responses to the S1509a tumor syngeneic to AJ mice and the chemical hapten, azobenzenearsonate, coupled onto the surface of syngeneic lymphoid cells. The intravenous injection of microliter amounts of anti-I-A alloantisera prevents the generation of immune T cells to either of the antigens employed. Kinetic analysis of the observed effect suggested that cellular interactions taking place at the time of antigen presentation during either immunization or challenge constituted the primary target of antiserum treatment. Finally, by using F1 hybrids, and immunizing these mice with antigen-coupled antigen-presenting cells of either parental types, it could be determined that anti-I-A antiserum was interacting primarily with cell surface structures involved in the presentation of nominal antigen to antigen-reactive cells. The general significance and potential application of these findings to therapeutic manipulations are also discussed.

ANTIGEN AND RECEPTOR STIMULATED REGULATION. THE RELATIONSHIP OF IDIOTYPE AND MHC PRODUCTS TO REGULATORY NETWORKS

ABSTRACT Antigen-specific suppressor thymus-derived (T) cells (T s ) are generated in A/J mice by the intravenous administration of azobenzenearsonate modified A/J spleen cells (ABA-spl). Discrete subcellular proteins have been obtained from ABA-specific suppressor T cells which can limit the in vivo development of ABA-specific DTH in A/J. Immunochemical analysis of such molecules has established that T s suppressor factor (T S F) bear H-2 encoded structures and determinants recognized by anti-idiotypic antibody. Furthermore all strains of mice tested produce ABA-specific T s after i.v. immunization with syngeneic ABA-spl. However, only the A strain or the allotype congenic C.AL-20 produces antibody with the cross-reactive idiotype (CRI) and the idiotype bearing T S F. B10.A (H-2 a ) which can make T S F active in B10.A, produces T S F which do not bear cross-reactive idiotypic determinants. ABA T s F, derived from T s , when administered to naive mice stimulates the development of T s2 capable of inhibiting ABA DTH. Furthermore, antibodies with CRI, when coupled to lymphocytes and administered intravenously, stimulate the development of specific T s . Anti CRI passively administered also was found to elicit T s capable of inhibiting the DTH reaction to ABA in A/J mice.