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Selective T-cell unresponsiveness, as measured by interleukin 2 (IL-2) synthesis upon challenge with antigen, was induced in SJL mice by ovalbumin (OVA) in incomplete or complete Freund's adjuvant administered i.p. or s.c. Ten days later, the mice were given booster injections of 100 micrograms of OVA/complete Freund's adjuvant. On day 20, lymph node and spleen cells were challenged in vitro with serial dilutions of OVA. There was an antigen-specific dose-dependent down regulation of IL-2 production and T-cell proliferation in lymph node T cells. Concomitantly, 100 micrograms of OVA up regulated IL-4 and, to a lesser extent, interferon gamma (IFN-gamma) production, particularly by spleen T cells. Altogether, these data indicate that the drop of IL-2 production and T-cell proliferation, as well as the up regulation of IL-4 and IFN-gamma production, are complex manifestations of an evolving T-cell response. The maturation of the T-cell response leads to the production of different patterns of lymphokines, which may be significantly affected, as desired, by dosage, timing, and route of immunization, as well as by the choice of adjuvants.

We have evaluated the ability of ovalbumin to induce T-cell-specific tolerance in SJL mice. A significant decrease of interleukin 2 in lymph-node culture supernatants from tolerant mice upon antigen stimulation was seen. Oral tolerization was less effective than i.p.- or s.c.-tolerization protocols. Transfer experiments of either splenic or lymph-node T cells from tolerant mice to naive mice definitely ruled out suppression as a mechanism involved in tolerant mice. Surprisingly, we found that, before the establishment of specific T-cell tolerance to ovalbumin, T cells from mice that will display tolerance were responsive and synthesized interleukin 2 upon antigen challenge in vitro. Thus, we concluded that anergy cannot account solely for the T-cell unresponsiveness in tolerant mice. Furthermore, although we cannot rule out the hypothesis that the T-cell unresponsiveness in tolerant mice can be explained by programmed cell death of ovalbumin-specific T cells, these data led us to speculate that T-cell "refractoriness" could explain the drop of interleukin 2 production in lymph-node T-cell culture supernatant from tolerant mice.