title: Combined CD4+ donor lymphocyte infusion and low-dose recombinant IL-2 expand FOXP3+ regulatory T cells following allogeneic hematopoietic stem cell transplantation.
abstract: CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) successfully control graft-versus-host-disease (GVHD) in animal models. In humans, incomplete reconstitution of Treg after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with chronic GVHD (cGVHD). Recent studies have demonstrated that interleukin (IL)-2 infusions expand Treg in vivo. However, the effectiveness of this therapy depends on the number of cells capable of responding to IL-2. We examined the effect of low-dose IL-2 infusions on Treg populations after HSCT in patients who also received infusions of donor CD4(+) lymphocytes. Utilizing FOXP3 as a Treg marker, we found that patients who received CD4+DLI concomitantly with IL-2 had greater expansion of Treg compared to patients who received IL-2 (P = .03) or CD4(+)DLI alone (P = .001). FOXP3 expression correlated with absolute CD4(+)CD25(+) cell counts. Moreover, expanded CD4(+)CD25(+) T cells displayed normal suppressive function and treatment with CD4(+)DLI and IL-2 was not associated with GVHD. This study suggests that administration of low-dose IL-2 combined with adoptive CD4(+) cellular therapy may provide a mechanism to expand Treg in vivo.
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zorn
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Mohseni
authors.forename: Haesook
authors.initials: H
authors.lastname: Kim
authors.forename: Fabrice
authors.initials: F
authors.lastname: Porcheray
authors.forename: Allison
authors.initials: A
authors.lastname: Lynch
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellucci
authors.forename: Christine
authors.initials: C
authors.lastname: Canning
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit