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FOXP3 mRNA does not specify human regulatory T cells

Posted by plosmedicine on 30 Mar 2009 at 23:58 GMT

Author: Michael Probst-Kepper
Institution: Hannover Medical School
Submitted Date: August 30, 2006
Published Date: August 31, 2006
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

The article by Faal et al. (PLoS Med. 2006; 3: e266) describes differences in the level of FOXP3 mRNA expression in the conjunctiva of patients with C. trachomatis infection. The authors suggest that their results may indicate a role for regulatory T cells in the resolution of conjunctival immune response, since FOXP3 mRNA remained elevated even if clinical disease signs were present in the absence of infection.
But suggestions about the function of regulatory T cells in diseases based only on the quantification of FOXP3 mRNA should be considered with great caution. According to the current state-of-the-art it is well established that FOXP3 does not specify human regulatory T cells since it is expressed at the mRNA and the protein levels to different extends (1-4). Thus, without quantification of FOXP3 protein at the single cell level in conjunction with reliable markers of human regulatory T cells, e.g. the recently identified lack of CD127 expression on regulatory T cells (5,6), the potential contribution or association of regulatory T cells with a disease cannot be assessed.

1.) Ziegler, S.F. FOXP3: Of Mice and Men. Annual Review of Immunology 24, 209-226 (2006).
2.) Gavin, M.A., Torgerson, T.R., Houston, E., deRoos, P., Ho, W.Y., Stray-Pedersen, A., Ocheltree, E.L., Greenberg, P.D., Ochs, H.D. & Rudensky, A.Y. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. PNAS 103; 6659-6664 (2006).
3.) Ocklenburg, F., Moharregh-Khiabani, D., Geffers, R., Janke, V., Pfoertner, S., Garritsen, H., Groebe, L., Klempnauer, J., Dittmar, K.E., Weiss, S., Buer & Probst-Kepper, M. UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells. Lab Invest 86, 724-737 (2006).
4.) Mantel, P.Y., Ouaked, N., Ruckert, B., Karagiannidis, C., Welz, R., Blaser, K. & Schmidt-Weber, C.B. Molecular Mechanisms Underlying FOXP3 Induction in Human T Cells. J Immunol 176, 3593-3602 (2006).
5.) Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S.I., Nanan, R., Kelleher, A. & de St.Groth, B.F. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203: 1693-700 (2006).
6.) Liu, W., Putnam, A.L., Xu-yu, Z., Szot, G.L., Lee, M.R., Zhu, S., Gottlieb, P.A., Kapranov, P., Gingeras, T.R., de St.Groth, B.F., Clayberger, C., Soper, D.M., Ziegler, S.F. & Bluestone, J.A. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 203: 1701-11 (2006).

No competing interests declared.