Alloantigen pretreatment induces a down-regulation of the in vivo subsequent development of cytotoxic T lymphocytes directed against linked alloantigens.

Abstract

In the present study, we describe a new regulatory system that influences the in vivo development of cytotoxic T lymphocytes (CTL) and that could be related to epitopic suppression. Epitopic suppression has been previously shown to occur when carrier-primed mice are subsequently immunized with a "new" epitope coupled to the priming carrier. The suppression specifically inhibited the antibody response to the "new" epitope without affecting the secondary antibody response to the carrier. In this report, using a carrier/hapten-carrier type of immunization protocol, we have demonstrated that a similar regulatory system could also affect the induction of CTL directed against allogeneic cells. Priming mice with an alloantigen 1 (carrier) inhibits the induction of alloantigen 2 (hapten)-specific cytotoxic responses when the alloantigen 2 is presented in association with the alloantigen 1 on an F1 stimulator cell (hapten-carrier conjugate). This has been demonstrated by the specific decrease of anti-H-2b or anti-H-2d CTL responses generated in C3H/He mice (H-2k) previously primed with, respectively, H-2d or H-2b spleen cells before immunization with F1 (H-2d x b) spleen cells. This suppression of the CTL responses against the second immunizing alloantigen is associated with a strong CTL response against the first priming alloantigen. The induction of the suppression is dependent on the dose of H-2d spleen cells administered before immunization with F1 spleen cells and is not related to antigen elimination since a strong suppression of the CTL response against H-2b antigens is shown following immunization with a mixture of F1 cells and H-2b-bearing cells of H-2d-primed animals.