Allogeneic T regulatory cell–mediated transplantation tolerance in adoptive therapy depends on dominant peripheral suppression and central tolerance
Year: 2009
Type: article
Abstract: T regulatory cells (Tregs) represent agents to mediate tolerance to allografts so that the use of immunosuppressive drugs is avoided. In this regard, we previously demonstrated that the adoptive transfer of allogeneic Tregs into IL-2Rbeta(-/-) mice prevented autoimmunity and led to allograft tolerance. Here, we investigated the requirements and mechanisms that favor this long-lasting tolerance. The most potent tolerance required exact matching of all alloantigens between the adoptively transferred allogeneic Tregs and allogeneic skin grafts, but tolerance to such allografts that lacked expression of major histocompatibility complex class I or II molecules also occurred. Thus, Tregs are not required to directly recognize major histocompatibility complex class II alloantigens to suppress skin transplant rejection. Depletion of allogeneic Tregs substantially, but not completely, abrogated this form of tolerance. However, thymocytes from allogeneic Treg adoptively transferred IL-2Rbeta(-/-) mice did not reject the corresponding allogeneic skin graft in secondary Scid recipients. Consistent with a requirement for a deletional mechanism in this IL-2Rbeta(-/-) model, a small number of wild-type T cells readily abrogated the immune tolerant state. Collectively, these findings indicate that full tolerance induction is largely dependent on substantial Treg-mediated suppression and thymic deletion of alloreactive T cells and may represent general conditions for Treg-mediated transplantation tolerance.
Source: Blood
Institution: University of Miami
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2146321849