Concomitant enhancement of the response to Mls-1a antigens and the induction of post-thymectomy autoimmune gastritis in BALB/c mice

SUMMARY We examined the role of Mis antigens in the induction of autoimmune gastritis (AIG) in BALB/c and DBA/2 mice subjected to thymeclomy. The prevalence of AIG in Mls-lb mice which underwent thymectomy on day 3 after birth (3d-Tx) was 78% (mean), while in Mis-1a DBA/2 mice it was < 6%. Whereas AlG-negative 3d-Tx DBA/2 mice produced 2-mercaptoethanol (2-MF.)–sensitive anti-parietal cell autoantibody. AIG-positive BALB/c mice made 2–ME-resistant anti-parietal cell autoantibody. In addition, the prevalence of AIG in 3d-Tx BALB/c mice which were rendered tolerant to M Is-1a antigens by injection of bone marrow cells from (BALB/c ± DBA/2)F1 mice within 24 h after birth was decreased compared with the non-tolerant control mice: the prevalence being 80% in the controls and 30% in the tolerant animals. Thus, the activation of helper T cells, including T cells responding to Mls-1a antigens and including immunoglobulin class switch, appeared to be closely associated with the induction of AIG. Flowcytometric analysis confirmed that C'D4- Vβ6 T cells had increased in the regional lymph nodes of the stomach in AIG mice. However, an increase in the number of Vβll T cells, which are known to increase in 3d-Tx mice, occurred in the CD8, but not in the CD4 T cell population. Injection of MoAb to L3T4. but not Lyt2. Vβ6-or Vβ8–TCR, into 3d-Tx BALB/c and syngeneic nude mice which had received spleen cells of 3d-Tx BALB/c mice bearing AIG completely abrogated the development of AIG. despite there being remarkable decreases in T cells expressing relevant markers to the injected antibodies in all the mice. These findings suggest that the increase of VbT6+L3T4+ T cells in AIG mice was concomitant with the activation of A IG-inducing Vβ6- L3T4+ T cells.