No abstract

EX645 is a derivative of Salmonella typhi Ty21a which carries a plasmid specifying production of Vibrio cholerae O antigen. When cultured with exogenous galactose to overcome the galE defect of the vector, EX645 also synthesizes S. typhi O antigen, and this can result in the masking of the shorter V. cholerae O antigen on the bacterial surface. To determine whether the potential for such masking at least partly underlies the inconsistency of anti-V. cholerae responses elicited by EX645, a derivative of this strain has been isolated, characterized, and tested for immunogenicity in human volunteers. EX880 has an rfb defect which prevents synthesis of S. typhi O antigen, and consequently V. cholerae O antigen is still detectable on the surface of the clone following growth in the presence of galactose. Compared with EX645, EX880 more consistently elicited significant rises in serum bactericidal antibody levels, although individual responses within a cohort still varied widely.

Mice injected with rat erythrocytes (RBC) produce RBC autoantibodies and antibodies against rat RBC. Transfer of spleen cells from autoantibody-producing mice to syngeneic recipients before the series of rat RBC injections causes a significant delay in autoantibody production although the response against rat RBC is elevated. Here it is shown that antibodies against rat RBC are markedly increased in recipients exposed to 350 rad of whole-body irradiation before transfer of spleen cells and the injections of rat RBC. In contrast, autoantibody production remained significantly suppressed. This shows that the anti-rat RBC response is regulated, at least in part, by cells in normal mice that are abrogated by 350 rad of whole-body irradiation.

Summary. Erythrocyte autoantibodies and autoantibody-specific suppressor cells are elicited in mice injected with rat erythrocytes. Here it is shown, first, that modified rat erythrocytes elicit suppressor cells independently of autoantibody production. Haemoglobin-free membranes of rat erythrocytes. but not soluble lysates of rat erythrocytes, elicited autoantibodies and suppressor cells. Solubilization of these rat erythrocyte membranes with solutions of Triton-X-114 produced membrane fractions which induced autoanti body-specific suppression in the absence of detectable autoantibody production. These results are compatible with the view that the activation of suppressor cells in this model involves recognition of structures on the rat erythrocytes. Secondly, trinitrophenyl (TNP) was attached to rat erythrocytes in various doses in attempts to make the immunogenicity of TNP similar to that of the cross-reactive determinants on rat and mouse erythrocytes, to determine whether TNP-specific suppressor cells were produced. The results show that at various doses of TNP, including those at which antibody production to TNP could not be detected, rat erythrocytes coated with TNP induced aiitoantibody-specific suppressor cells but not suppressor cells with specificity for antibodies to TNP.