Induction of Peripheral Tolerance in Neonatally Thymectomized Mice by Immunization 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 consequence of altered immunoregulatory mechanisms, we set out to determine the immunological status of these mice and their capacity to acquire antigen-specific peripheral tolerance. The latter was assessed by the capacity 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 CD8+T cells and a reduced lymphocyte proliferative response to PHA, but a normal contact sensitivity response to TNCB. After treatment of the skin with DMBA these mice failed to develop contact sensitivity to TNCB. Adoptive transfer of splenocytes from these mice to naive mice transfered antigen-specific suppression, irrespective of whether the 3dnTx 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 TNCB was retained. These results suggest that precursor T cells which mediate suppression to antigens such as TNCB are present in 3dnTx mice and that these cells are likely to have developed in the thymus and exported to the periphery before 3 days after birth.