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Co-expression of TNFR2 and CD25 identifies more of the functional CD4(+)FOXP3(+) regulatory T cells in human peripheral blood

  1. Author:
    Chen, X.
    Subleski, J. J.
    Hamano, R.
    Howard, O. M. Z.
    Wiltrout, R. H.
    Oppenheim, J. J.

  2. Author Address

    [Chen, Xin] NCI Frederick, BSP, SAIC Frederick Inc, Mol Immunoregulat Lab,CIP, Frederick, MD 21702 USA. [Subleski, Jeffrey J.; Wiltrout, Robert H.] NCI Frederick, Expt Immunol Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Hamano, Ryoko; Howard, O. M. Zack; Oppenheim, Joost J.] NCI Frederick, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.;Chen, X, NCI Frederick, BSP, SAIC Frederick Inc, Mol Immunoregulat Lab,CIP, POB 8,Bldg 560,Room 31-19, Frederick, MD 21702 USA.;chenxin@mail.nih.gov
    1. Year: 2010
    2. Date: Apr
    3. Epub Date: 2/4/2010
  2. Journal: European Journal of Immunology
    1. 40
    2. 4
    3. Pages: 1099-1106
  4. Type of Article: Article
  5. ISSN: 0014-2980
  1. Abstract:

    Previously, we found that co-expression of CD25 and TNFR2 identified the most suppressive subset of mouse Treg. In this study, we report that human peripheral blood (PB) FOXP3(+) cells present in CD25(high), CD25(low) and even CD25(-) subsets of CD4(+) cells expressed high levels of TNFR2. Consequently, TNFR2-expressing CD4(+)CD25(+) Treg included all of the FOXP3(+) cells present in the CD4(+)CD25(high) subset as well as a substantial proportion of the FOXP3(+) cells present in the CD4(+)CD25(low) subset. Flow cytometric analysis of PB identified five-fold more Treg, determined by FOXP3 expression, in the CD4(+)CD25(+)TNFR2(+) subset than in the CD4(+)CD25(high) subset. In addition, similar levels of FOXP3(+) cells were identified in both the CD4(+)CD25(+)TNFR2(+) and CD4(+)CD25(+) CD127(low/-) subsets. Furthermore, the CD4(+)CD25(+)TNFR2(+) subset expressed high levels of CTLA-4, CD45RO, CCR4 and low levels of CD45RA and CD127, a phenotype characteristic of Treg. Upon TCR stimulation, human PB CD4(+)CD25(+)TNFR2(+) cells were anergic and markedly inhibited the proliferation and cytokine production of co-cultured T-responder cells. In contrast, CD4(+)CD25(+)TNFR2(-) and CD4(+)CD25(-)TNFR2(+) T cells did not show inhibitory activity. As some non-Treg express TNFR2, the combination of CD25 and TNFR2 must be used to identify a larger population of human Treg, a population that may prove to be of diagnostic and therapeutic benefit in cancer and autoimmune diseases.

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External Sources

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  2. DOI: 10.1002/eji.200940022
  3. PMID: 20127680
  4. View record in Web of Science®
  5. WOS: 000277210800020

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  1. Fiscal Year: FY2009-2010
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