- Paper Report
- Open Access
Regulatory T cells and GVHD
- Ranjeny Thomas1
© Biomed Central Ltd 2001
- Received: 27 July 2001
- Published: 16 August 2001
- regulatory T cells
So-called 'suppressor' or 'regulatory' T cells are thought to prevent activation, in the periphery, of two cell types: antigen-presenting cells (APCs) that present endogenously processed self-antigens, and self-reactive T cells that have escaped thymic deletion (see Additional information ). It was found that T cells with the phenotype CD4+CD25+ can prevent autoimmune disease in the context of neonatal thymectomy when adoptively transferred (see Additional information ). This paper investigated whether T cells of the same phenotype could transfer tolerance for alloantigen in both in vitro and in vivoallogeneic T-cell transfer models of graft-versus-host disease (GVHD).
T-cell proliferation occurred in vitro when APCs were incubated with allogeneic T cells in a mixed lymphocyte reaction (MLR). When CD40L was blocked, tolerance to the alloantigen occurred. When the T cells were restimulated with the same APCs in a secondary MLR, proliferation was suppressed. Depletion of CD4+CD25+ T cells prior to the primary MLR abrogated the induction of hyporesponsiveness to alloantigen rechallenge in the secondary MLR after anti-CD40L costimulatory blockade in the primary allogeneic MLR. Moreover, purified CD4+CD25+T cells in high concentrations suppressed a primary MLR.
In vivo, mice inoculated with T cells from an MLR cultured without blocking antibody all died from GVHD, whereas adoptive transfer of T cells cultured in allogeneic MLR in the presence of either anti-B7 or anti-CD40L monoclonal antibody did not induce GVHD. In a similar fashion to the in vitro experiments, depletion of CD4+CD25+ T cells from MLR before transfer abrogated protection against GVHD.
Adoptive transfer, MLR
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