title: Relative resistance of human CD4(+) memory T cells to suppression by CD4(+) CD25(+) regulatory T cells.
abstract: Successful expansion of functional CD4(+) CD25(+) regulatory T cells (T(reg)) ex vivo under good manufacturing practice conditions has made T(reg) -cell therapy in clinical transplant tolerance induction a feasible possibility. In animals, T(reg) cells home to both transplanted tissues and local lymph nodes and are optimally suppressive if active at both sites. Therefore, they have the opportunity to suppress both naïve and memory CD4(+) CD25(-) T cells (Tresp). Clinical transplantation commonly involves depleting therapy at induction (e.g. anti-CD25), which favors homeostatic expansion of memory T cells. Animal models suggest that T(reg) cells are less suppressive on memory, compared with naïve Tresp that mediate allograft rejection. As a result, in the context of human T(reg) -cell therapy, it is important to define the effectiveness of T(reg) cells in regulating naïve and memory Tresp. Therefore, we compared suppression of peripheral blood naïve and memory Tresp by fresh and ex vivo expanded T(reg) cells using proliferation, cytokine production and activation marker expression (CD154) as readouts. With all readouts, naïve human Tresp were more suppressible by approximately 30% than their memory counterparts. This suggests that T(reg) cells may be more efficacious if administered before or at the time of transplantation and that depleting therapy should be avoided in clinical trials of T(reg) cells.
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Afzali
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Mitchell
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Scottà
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Canavan
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: F C
authors.initials: FC
authors.lastname: Edozie
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Fazekasova
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Lord
authors.affiliation: Department of Immunobiology, King's College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: John
authors.affiliation: Department of Hematology, King's College London, London, UK.
authors.forename: L D
authors.initials: LD
authors.lastname: Barber
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Hernandez-Fuentes
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
authors.affiliation: MRC Centre for Transplantation and National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D015704:CD4 Antigens / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit