INDUCTION OF PERIPHERAL TOLERANCE IN NEONATALLY THYMECTOMIZED MICE BYIMMUNIZATION THROUGH CHEMICAL CARCINOGEN-ALTERED SKIN

BALB/c mice thymectomized 3 days after birth (3dnTx) are prone to the development of autoimmune gastritis. As this outcome may be a conseque nce of altered immunoregulatory mechanisms, we set out to determine th e immunological status of these mice and their capacity to acquire ant igen-specific peripheral tolerance. The latter was assessed by the cap acity of these mice to suppress a contact sensitivity response to 2,4, 6-trinitrochlorobenzene (TNCB) following treatment of the skin by the carcinogen, DMBA, The 3dnTx mice had a reduced number of CD4(+) and CD 8(+) T cells and a reduced lymphocyte proliferative response to PHA, b ut a normal contact sensitivity response to TNCB, After treatment of t he skin with DMBA these mice failed to develop contact sensitivity to TNCB, Adoptive transfer of splenocytes from these mice to naive mice t ransfered antigen-specific suppression, irrespective of whether the 3d nTx mice had developed autoimmune gastritis. We conclude that despite thymectomy at day 3 and the attendant immunosuppression, the capacity of BALB/c mice to generate antigen-specific peripheral tolerance to TN CB was retained. These results suggest that precursor T cells which me diate suppression to antigens such as TNCB are present in 3dnTx mice a nd that these cells are likely to have developed in the thymus and exp orted to the periphery before 3 days after birth. (C) 1998 Academic Pr ess.