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- Publisher
- Wiley
- Copyright
- Copyright © 2007 Wiley Subscription Services
- ISSN
- 0020-7136
- eISSN
- 1097-0215
- DOI
- 10.1002/ijc.23001
- pmid
- 17691114
- Publisher site
- See Article on Publisher Site
Abstract
Circulating human CD4+CD25highFoxp3+ T cell populations (Treg) may contain activated CD4+CD25+ T cells interfering with Treg evaluation. To gain insights into the phenotypic and functional characteristics of Treg in patients with cancer, we have analyzed CD4+CD25high populations at the clonal level. Single‐cell sorted (SCS) CD4+CD25high T cells obtained from PBMC of normal controls (NC) or patients with squamous cell carcinoma of the head and neck (HNSCC) were plated at 1 cell/well in 96 well plates and expanded with anti‐CD3/anti‐CD28 Abs and 1,000 IU IL‐2/mL in the presence or absence of rapamycin (1 nM). All generated clones were evaluated for the phenotype by flow cyometry and suppressor function in CFSE‐based proliferation assays. Clones had heterogeneous CD25 expression levels. Cloning efficiency of CD4+CD25high T cells was low. CD25high clones expressed CTLA‐4, Foxp3, CD62L, but little GITR and suppressed proliferation of autologous CD4+CD25− responder cells. Clones of activated CD4+CD25interm./low cells expressed intermediate to high levels of GITR and HLA‐DR and did not suppress proliferation of responder cells. The number, suppressor phenotype and function of CD25high Treg clones were significantly enhanced in HNSCC patients relative to NC (p ≤ 0.001). CD4+CD25+ populations comprise phenotypically and functionally distinct subsets of CD25+ cells. Only a small fraction of these activated CD4+ T cells are potent suppressor cells characterized by high expression levels of CD25, Foxp3, CTLA‐4 and CD62L. The number of expandable Treg is increased in HNSCC patients. © 2007 Wiley‐Liss, Inc.
Journal
International Journal of Cancer – Wiley
Published: Jan 1, 2007
Keywords: ; ; ; ;