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

We examined the role of Mls antigens in the induction of autoimmune gastritis (AIG) in BALB/c and DBA/2 mice subjected to thymectomy. The prevalence of AIG in Mls-1^b mice which underwent thymectomy on day 3 after birth (3d-Tx) was 78% (mean), while in Mls-1^a DBA/2 mice it was < 6%. Whereas AIG-negative 3d-Tx DBA/2 mice produced 2-mercaptoethanol (2-ME)-sensitive antiparietal 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 Mls-1^a antigens by injection of bone marrow cells from (BALB/c x 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-1^a antigens and including immunoglobulin class switch, appeared to be closely associated with the induction of AIG. Flow cytometric analysis confirmed that CD4-Vβ6 T cells had increased in the regional lymph nodes of the stomach in AIG mice. However, an increase in the number of Vβ11 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 Vβ6⁺ L3T4⁺ T cells in AIG mice was concomitant with the activation of AIG-inducing Vβ6^- L3T4⁺ T cells.