Epinephrine augments specific T-cell responses to antigen in C57BL/6 (H-2b) weak-responder mice by a CD8+...

Stress has been implicated as a factor in the pathogenesis of autoimmune disorders. In order to determine the effect of adrenergic stress on immune responses in vivo, C57BL/6 (B6; H-2b) mice, which respond weakly to hen-egg lysozyme (HEL), were immunized on day 0 with HEL (50-200 microg s.q.) and subsequently injected with epinephrine (EPI; 0.1-0.5 mg/kg s.q.) daily for up to 10 days. Controls included A/J mice (H-2k) which respond strongly to HEL. In some experiments, B6 mice were depleted of CD4+ or CD8+ lymphocytes by monoclonal antibody treatment in vivo, prior to immunization with HEL, and injection with EPI. On day 10, single cell suspensions of draining lymph nodes (LN) and spleen were examined for immune phenotype, proliferative responses to HEL, and lymphokine production. Minimal specific proliferative responses were detected in B6 mice compared to A/J mice. However, lymphocyte proliferation increased in HEL-immunized EPI-treated B6 mice but not in the A/J mice. IL-2-mediated proliferation and IL-2 secretion were both increased in the HEL-immunized EPI-treated B6 mice. The depletion of CD8+ but not CD4+ lymphocytes in vivo abrogated the effects of EPI, whereas adoptive transfer of naive CD8+ splenocytes to the CD8-depleted mice restored specific responses in the HEL-immunized EPI-treated animals. We conclude that EPI augments antigen-specific T-cell responses to HEL in B6 mice by a CD8+ T-cell-dependent mechanism.