Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome

• Published in: Leukemia Vol. 23; no. 7; pp. 1288 - 1296
• Main Authors: Zou, J X, Rollison, D E, Boulware, D, Chen, D-T, Sloand, E M, Pfannes, L V, Goronzy, J J, Bai, F, Painter, J S, Wei, S, Cosgrove, D, List, A F, Epling-Burnette, P K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2009; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Antigens; Autoimmunity; Biological and medical sciences; Blood & organ donations; Bone marrow; Cancer; Cancer Research; Care and treatment; Case-Control Studies; CD4 antigen; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - immunology; CD45RA antigen; CD8 antigen; Cell activation; Cell cycle; Cell Proliferation; Critical Care Medicine; Depletion; Flow Cytometry; Health aspects; Hematologic and hematopoietic diseases; Hematology; Hematopoiesis; Homeostasis; Humans; Immunologic Memory; Immunological memory; Immunology; Immunosenescence; Immunosuppressive agents; Immunotherapy; Intensive; Internal Medicine; L-selectin; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes T; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - immunology; Myelodysplastic Syndromes - pathology; Oncology; original-article; Patients; Phenotypes; Physiological aspects; Risk factors; T cells; T-Lymphocyte Subsets; United States; United States > US; immunosuppressive therapy; T lymphocytes; homeostasis; aging; myelodysplastic syndrome; bone marrow; Human; Memory disorder; Cognitive disorder; CD4 T lymphocyte; Hematology; Ageing; Homeostasis; Malignant hemopathy; Myelodysplastic syndrome; Memory lymphocyte; T-Lymphocyte; Bone marrow; Immunosenescence; Immunosuppressive agent; Age; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.14

Response to immunosuppressive therapy (IST) in younger patients with myelodysplastic syndrome (MDS) has been linked to a T-cell-dominant autoimmune process that impairs hematopoiesis. Analysis of the age-adjusted CD4:CD8 ratio in 76 MDS patients compared with 54 healthy controls showed that inadequate CD4+, rather than expansion of CD8+ T cells, was associated with a lower ratio in a group that included both lower and higher risk MDS patients defined by the International Prognostic Scoring System. In younger MDS patients, naive and memory phenotypes defined by CD45RA and CD62L display showed depletion of naive CD4+ and CD8+ T cells, suggesting a possible relationship to IST responsiveness. To determine the correlation between T-cell subset distribution, T-cell turnover and autoimmunity, a cohort of 20 patients were studied before and after IST. The CD4:CD8 ratio correlated inversely with the proliferative T-cell index before treatment in IST-responsive patients, suggesting that proliferation may be linked to accelerated CD4+ T-cell turnover and hematopoietic failure. Our data show seminal findings that both CD4+ and CD8+ T-cell subsets are dysregulated in MDS. Association between these T-cell defects and response to IST suggests that aberrant T-cell homeostasis and chronic activation are critical determinants influencing autoimmune hematopoietic suppression in younger patients.