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The Journal of Immunology, 2008, 180, 6437
Copyright © 2008 by The American Association of Immunologists, Inc.

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Comment on "Homeostasis of the Naive CD4+ T Cell Compartment during Aging"

Andreas Thiel and Siegfried Kohler

Clinical Immunology Group, Deutsches Rheuma-Forschungszentrum, Charitéplatz 1, D-10117 Berlin, Germany Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, D-13353 Berlin, Germany

Recently The Journal of Immunology published an article by Kilpatrick et al. (1) following up our own articles introducing and characterizing CD31+ thymicnaive Th cells and CD31– centralnaive Th cells (2, 3). Kilpatrick et al. have performed an elegant longitudinal study and demonstrated for the first time that the CD45RA+CD31+CD4+ subset undergoes in vivo proliferation without immediate loss of CD31 resulting in CD45RA+CD31+ proliferative offspring. Furthermore, they have examined CD4+ T cell subsets defined by CD45RA and CD31 expression for their TCR repertoire.

In the Discussion on page 1505, Kilpatrick et al. cite one of our previous papers (3) and discuss this in the context of their own results: "Although our results are in direct contrast to Kohler et al. (43), who find strongly perturbed repertories in both naive CD4+ T cell subsets as early as 24 years of age, we did not examine TCR Vβ repertoires in the elderly, defined as ≥65 years of age, and we concede that the situation may be quite different at more advanced ages, as found by Naylor et al. (13)."

However, in the previous sentence the citation of our paper (3) is misleading. We did not find strongly perturbed repertoires in both naive CD4+ T cell subsets. Rather, our data demonstrated a polyclonal repertoire for the majority of samples obtained from CD31+ thymicnaive CD4+ T cells while strongly perturbed repertoires were demonstrated frequently in CD31– centralnaive CD4+ T cells. Thirty-four of 43 Vβ-Jβ-chain combinations (79%) analyzed from CD31 central naive CD4+ T cells were oligoclonal, compared with 6 of 43 (14%) in CD31+ thymicnaive CD4+ T cells (p ≤ 0.001).

This point is one of the main messages of our article (3) and is of central importance for understanding the role we propose for the aforementioned two subsets of naive human CD4+ T cells.

References

  1. Kilpatrick, R. D., T. Rickabaugh, L. E. Hultin, P. Hultin, M. A. Hausner, R. Detels, J. Phair, B. D. Jamieson. 2008. Homeostasis of the naive CD4+ T cell compartment during aging. J. Immunol. 180: 1499-1507. [Abstract/Free Full Text]
  2. Kimmig, S., G. K. Przybylski, C. A. Schmidt, K. Laurisch, B. Möwes, A. Radbruch, A. Thiel. 2002. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195: 789-894. [Abstract/Free Full Text]
  3. Kohler, S., U. Wagner, M. Pierer, S. Kimmig, B. Oppmann, B. Möwes, K. Jülke, C. Romagnani, A. Thiel. 2005. Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults. Eur. J. Immunol. 35: 1987-1994. [Medline]



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R. D. Kilpatrick, T. Rickabaugh, and B. D. Jamieson
Response to Comment on "Homeostasis of the Naive CD4+ T Cell Compartment during Aging"
J. Immunol., May 15, 2008; 180(10): 6437 - 6437.
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