COMPLETE FREUND ADJUVANT-INDUCED T-CELLS PREVENT THE DEVELOPMENT AND ADOPTIVE TRANSFER OF DIABETES IN NONOBESE DIABETIC MICE

Insulin-dependent diabetes mellitus is an autoimmune disease that is characterized by the destruction of insulin-producing beta cells in the islet of Langerhans. We have recently reported that the induction of the disease in nonobese diabetic (NOD) mice can be prevented by a single injection of CFA. In this study, we have explored the cellular basis and the time course of the disease protection. Since CFA contains a mycobacterial cell wall that has adjuvant property, we investigated the protective role of mycobacteria in young NOD mice. Mice injected with Mycobacterium tuberculosis or Mycobacterium bovis (BCG vaccine) at 4 wk of age were also found to be protected from diabetes. We have found that complete protection from diabetes is only achieved by administration of CFA between 4 and 10 wk of age. Draining lymph node cells or spleen cells from CFA-treated NOD mice transfer the protection. Adoptive transfer of spleen cells from CFA-treated mice with spleen cells from acutely diabetic mice delayed the induction of disease into irradiated recipient mice. CFA-treated old NOD mice were also resistant to passive transfer of disease by spleen cells from acutely diabetic mice. Depletion of the Thy 1.2+ cells or CD4+-bearing T cells abrogated the protection. However, disease can be induced in the protected mice by cyclophosphamide treatment. We also found that thymocytes from NOD mice responded only weakly to mitogen Con A. CFA treatment, however, restored the ability of these cells to respond to Con A. Finally, our results suggest that T cells induced after CFA treatment of NOD mice prevent both the induction and effector phases of the disease.