In vivo expansion of CD4+CD45RO-CD25+ T cells expressing foxP3 in IL-2-treated HIV-infected patients
| Autor: | Steve C. Berg, Richard T. Davey, Yunden Badralmaa, Meena S. Ramchandani, April Powers, H. Clifford Lane, Tomozumi Imamichi, Hiromi Imamichi, Ven Natarajan, Barbara K. Hahn, Joseph A. Kovacs, Julia A. Metcalf, Jean M. Shen, Ethan M. Shevach, Irini Sereti |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Interleukin 2 medicine.medical_treatment T cell Population Gene Expression Apoptosis HIV Infections chemical and pharmacologic phenomena Biology Cohort Studies Interleukin 21 T-Lymphocyte Subsets medicine Humans IL-2 receptor education Cell Proliferation education.field_of_study T-cell receptor FOXP3 Forkhead Transcription Factors Receptors Interleukin-2 hemic and immune systems General Medicine Middle Aged Molecular biology Recombinant Proteins DNA-Binding Proteins Phenotype Cytokine medicine.anatomical_structure Immunology Interleukin-2 Leukocyte Common Antigens Immunologic Memory Follow-Up Studies Research Article medicine.drug |
| Zdroj: | Journal of Clinical Investigation. 115:1839-1847 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci24307 |
| Popis: | Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4+CD45RO–CD25+ cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4+CD45RO–CD25+ cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45RO–CD25– or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25+ cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45RO+CD25+high cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4+CD45RO–CD25+ cells that express high levels of foxP3 but exert weak suppressive function. These CD4+CD25+ cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4+ T cell pool. |
| Databáze: | OpenAIRE |
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