Your browser doesn't support javascript.
loading
Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD.
Alho, Ana C; Kim, Haesook T; Chammas, Marie J; Reynolds, Carol G; Matos, Tiago R; Forcade, Edouard; Whangbo, Jennifer; Nikiforow, Sarah; Cutler, Corey S; Koreth, John; Ho, Vincent T; Armand, Philippe; Antin, Joseph H; Alyea, Edwin P; Lacerda, Joao F; Soiffer, Robert J; Ritz, Jerome.
Afiliação
  • Alho AC; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal;
  • Kim HT; Department of Biostatistics and Computational Biology, and Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA; and Harvard Chan School of Public Health, Boston, MA.
  • Chammas MJ; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA;
  • Reynolds CG; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA;
  • Matos TR; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Forcade E; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Whangbo J; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Nikiforow S; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Cutler CS; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Koreth J; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Ho VT; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Armand P; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Antin JH; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Alyea EP; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Lacerda JF; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal;
  • Soiffer RJ; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA;
  • Ritz J; Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA; and.
Blood ; 127(5): 646-57, 2016 Feb 04.
Article em En | MEDLINE | ID: mdl-26670634
The development and maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) requires the balanced reconstitution of donor-derived CD4 regulatory T cells (CD4Tregs) as well as effector CD4 (conventional CD4 T cells [CD4Tcons]) and CD8 T cells. To characterize the complex mechanisms that lead to unbalanced recovery of these distinct T-cell populations, we studied 107 adult patients who received T-replete stem cell grafts after reduced-intensity conditioning. Immune reconstitution of CD4Treg, CD4Tcon, and CD8 T cells was monitored for a 2-year period. CD3 T-cell counts gradually recovered to normal levels during this period but CD8 T cells recovered more rapidly than either CD4Tregs or CD4Tcons. Reconstituting CD4Tregs and CD4Tcons were predominantly central memory (CM) and effector memory (EM) cells and CD8 T cells were predominantly terminal EM cells. Thymic generation of naive CD4Tcon and CD8 T cells was maintained but thymic production of CD4Tregs was markedly decreased with little recovery during the 2-year study. T-cell proliferation was skewed in favor of CM and EM CD4Tcon and CD8 T cells, especially 6 to 12 months after HSCT. Intracellular expression of BCL2 was increased in CD4Tcon and CD8 T cells in the first 3 to 6 months after HSCT. Early recovery of naive and CM fractions within each T-cell population 3 months after transplant was also strongly correlated with the subsequent development of chronic graft-versus-host disease (GVHD). These dynamic imbalances favor the production, expansion, and persistence of effector T cells over CD4Tregs and were associated with the development of chronic GVHD.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Linfócitos T Reguladores / Transplante de Células-Tronco Hematopoéticas / Linfócitos T CD8-Positivos / Doença Enxerto-Hospedeiro Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Linfócitos T Reguladores / Transplante de Células-Tronco Hematopoéticas / Linfócitos T CD8-Positivos / Doença Enxerto-Hospedeiro Idioma: En Ano de publicação: 2016 Tipo de documento: Article