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Immunologic Reactions to Haptens on Autologous Carriers

II Induction of Hapten-Specific Tolerance and Correlations Between Antibody Response and Antigen-Driven Cell Proliferation in Vitro¹

Division of Clinical Immunology, Departments of Medicine and Microbiology, University of Colorado Medical Center, Denver, Colorado 80220

Abstract

Specific tolerance to the hapten NIP was induced in mice with a highly substituted conjugate the NIP-MGG (NIP-mouse -globulin). A correlation was made between tolerance at the serum level (as measured by the absence of NIP antibody) and tolerance at the cellular level as measured by absence of antigen-specific DNA synthesis. Different schedules were used for tolerance induction. Hapten-specific tolerance could be induced if soluble NIP-MGG was injected from 8 days before to 2 days after immunogen. At these times, tolerance was seen by both depression of serum anti-NIP antibody and suppression of antigen-driven DNA synthesis in vitro.

Both partial cross-stimulation and partial cross-tolerance were seen. In cross-stimulation, cells from mice immunized with NIP-MSA responded in vitro to NIP-MGG-this response was greatly reduced if the mice were also tolerized in vivo with soluble NIP-MGG. In cross-tolerance, cells from mice immunized with NIP-MSA and tolerized with NIP-MGG showed a reduced response to NIP-MSA in vitro.

We interpret these reults to mean that NIP-specific cells were generated in vivo by immunization, that these cells also responded to hapten in vitro, and that they could also be tolerized in vivo. In addition, however, there are cells specific for new antigenic determinants (NAD) formed by coupling NIP to carriers. These NAD-specific cells can also be generated in vivo and stimulated in vitro but are not susceptible to cross-stimulation or cross-tolerance by NIP on other carriers.

Footnotes

¹ This work was supported by National Institutes of Health Grant AM-10145.