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The anti-pancreatic immune reaction of genetically diabetic homozygote C57Bl/KsJ db/db mice was studied with an in vitro test using murine islet of Langerhans cells as target cells. C57Bl/KsJ db/db spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Together with this cell-mediated cytotoxicity, complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were found in the sera of these mice. A longitudinal study showed that this anti-pancreatic toxicity was detectable as early as the 10th day of life and lasted throughout the entire life span of the animal. None of these anomalies was found in control heterozygote mice.

Antilymphocyte sera (ALS), either allogeneic (for example, Lewis anti-August rat serum) or xenogeneic (the classic ALS), may retain the antigen used for the immunization of the animal producing the serum in the form of antigen-antibody complexes, at least when the animal is bled within the first 2 weeks following the last immunizing injection. Evidence for this has been obtained in vivo and in vitro. In vivo experiments showed that injection of Lewis anti-August serum to a normal Lewis rat can induce a delayed active immunization against the August strain. In vitro studies proved the presence of August antigens in the anti-August sera, by precipitation of the antigen-antibody complexes with 6 M urea, removal of the antibody by filtration, and demonstration that the filtrate specifically inhibits complement-dependent cytotoxicity of anti-August antibodies. The interpretation of a number of previous works on so-called passive enhancement of grafts or on various effects of ALS may have to be reconsidered on the basis of these findings.

This paper reviews the rosette inhibition test for the evaluation of antilymphocyte serum potency and reappraises the biological significance of the assay. Evidence is also presented which indicates the presence, in antilymphocyte serum, of immune complexes.