Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction

S Yamazaki, M Patel, A Harper… - Proceedings of the …, 2006 - National Acad Sciences
S Yamazaki, M Patel, A Harper, A Bonito, H Fukuyama, M Pack, KV Tarbell, M Talmor…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
Thymic-derived CD25+ CD4+ T regulatory cells (Tregs) suppress immune responses,
including transplantation. Here we evaluated the ability of dendritic cells (DCs) to expand
alloantigen-specific Tregs in the mixed leukocyte reaction (MLR) that develops from
polyclonal populations of T cells. The allogeneic DCs, when supplemented with IL-2 in the
cultures, were much more effective than bulk spleen cells in expanding the numbers of
Tregs. Likewise, DCs and not spleen cells were effective in sustaining expression of the …
Thymic-derived CD25+ CD4+ T regulatory cells (Tregs) suppress immune responses, including transplantation. Here we evaluated the ability of dendritic cells (DCs) to expand alloantigen-specific Tregs in the mixed leukocyte reaction (MLR) that develops from polyclonal populations of T cells. The allogeneic DCs, when supplemented with IL-2 in the cultures, were much more effective than bulk spleen cells in expanding the numbers of Tregs. Likewise, DCs and not spleen cells were effective in sustaining expression of the transcription factor Foxp3 in Tregs, but neither IL-2 nor CD80/86 was required for this effect in the cultures. On a per-cell basis, the DC-expanded, but not unexpanded, Tregs were more potent suppressors of a fresh MLR by CD25 CD4+ T cells. Suppression was 3- to 10-fold more active for MLRs induced by the original alloantigens than for third-party stimulators. When DC-expanded Tregs were introduced into sublethally irradiated hosts, the T cells suppressed graft-versus-host-disease induced by CD25 CD4+ T cells. Again, suppression was more active against the same mouse strain that provided the DCs to expand the Tregs. Therefore, alloantigen-selected Tregs are more effective suppressors of responses to major transplantation antigens, and these Tregs can be expanded from a polyclonal repertoire by DCs.
National Acad Sciences