Preferential induction of cell-mediated immunity by chemically modified sheep erythrocytes

Sheep red blood cells (SRBC) almost exclusively induce humoral antibodies when injected in saline into adult rats. Chemical modification of SRBC by either periodate oxidation or acetoacetylation resulted in preparations which provoked lower antibody responses than did normal SRBC, but induced much higher levels of delayed-type hypersensitivity. Furthermore, SRBC which had been both periodate oxidized and acetoacetylated induced even higher delayed responses, but were unable to stimulate detectable antibody formation. Thus, by two simple chemical treatments, SRBC have been converted from an antigen which predominantly induces humoral antibodies tc an antigen which exclusively provokes cell-mediated immunity. The chemically modified SRBC had some notable immunological properties. (I) Antigenically, they were still strongly agglutinated by anti-SRBC antiserum. (II) They very effectively induced delayed-type hypersensitivity when injected either in saline or Freund's complete adjuvant. (III) They lost their immunogenicity when lysed just prior to injection. (IV) They induced delayed-type hypersensitivity which cross-reacted with goose, rabbit and horse red blood cells, a result consistent with the notion that antigens cross-react more broadly at the cell-mediated immune level than at the antibody level. (V) Comparatively high levels of both humoral and cell-mediated immunity were achieved when a mixture of periodate oxidized SRBC and acetoacetylated SRBC was injected. The theoretical and practical implications of these findings are discussed.