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The Journal of Immunology, 2007, 178: 2612.
Copyright © 2007 by The American Association of Immunologists, Inc.

LETTERS TO THE EDITOR

Response to Comment on "Differential Usage of Cellular Niches by Cytomegalovirus versus EBV- and Influenza Virus-Specific CD8+ T Cells"

Ester M. M. van Leeuwen*,{dagger}, René A. W. van Lier* and Ineke J. M. ten Berge{dagger}

* Department of Experimental Immunology {dagger} Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Amsterdam, The Netherlands

In their letter, Schwanninger et al. (1) argue that the increase we have observed in total numbers of CD8+ T cells in CMV-seropositive individuals (2) could be a result of the fact that we studied immunosuppressed individuals. They show that in their cohort of healthy individuals the absolute number of CD8+ T cells was not significantly higher in CMV-seropositive individuals compared with CMV-seronegative individuals.

In our study, it was essential to study renal transplant recipients because under normal circumstances a primary infection in healthy individuals will not be recognized in time, if at all. This makes it impossible to document the effect of the entrance of new T cells with a different specificity in the existing memory pool.

In the discussion of our paper, we pointed out that we expect that our findings will likely be similar in healthy individuals but probably less pronounced. Indeed, when comparing absolute numbers of CD8+ T cells from CMV-seropositive and CMV-seronegative patients pretransplantation (i.e., before start of immunosuppressive therapy), we found that CMV-seropositive patients tend to have higher numbers (Fig. 4B in our paper (2)). Also, in Fig. 1B in the letter by Schwanninger et al., a tendency to higher CD8+ T cell numbers in CMV-seropositive healthy individuals is found (1). In both cohorts, the differences were not significant, but one should note that only small cohorts were studied. In fact, two older studies in much larger groups of healthy individuals revealed that CMV-seropositive individuals do have more CD8+ T cells (p ≤ 0.0001) (3, 4).

Thus, we conclude that CMV induces an increase in CD8+ T cell numbers also in healthy individuals, albeit less pronounced than in immunosuppressed individuals. As we already discussed (2), the changes in the CD8+ T cell population caused by CMV infection in immunosuppressed individuals are likely more distinct because these patients have higher viral loads and more frequent reactivations than healthy individuals. We adhere to our previous notion that different viruses have distinct impacts on the composition of the memory CD8+ T cell pool and that data obtained from studies with experimental viruses in mice cannot directly be extrapolated to the human system.

References

  1. Schwanninger, A., B. Weinberger, B. B. Grubeck-Loebenstein. 2007. Comment on "Differential usage of cellular niches by cytomegalovirus versus EBV- and influenza virus-specific CD8+ T cells.". J. Immunol. 178: 2611-2612. [Free Full Text]
  2. van Leeuwen, E. M. M., J. J. Koning, E. B. M. Remmerswaal, D. van Baarle, R. A. W. van Lier, I. J. M. ten Berge. 2006. Differential usage of cellular niches by cytomegalovirus versus EBV- and influenza virus-specific CD8+ T cells. J. Immunol. 177: 4998-5005. [Abstract/Free Full Text]
  3. Gratama, J. W., A. M. I. H. Naipal, M. A. P. Oosterveer, T. Stijnen, H. C. Kluin-Nelemans, L. A. Ginsel, G. J. den Ottolander, A. C. Hekker, J. D’Amaro, M. van der Giessen, H. J. Tanke. 1987. Effects of herpes virus carrier status on peripheral T lymphocyte subsets. Blood 70: 516-523. [Abstract/Free Full Text]
  4. Looney, R. J., A. Falsey, D. Campbell, A. Torres, J. Kolassa, C. Brower, R. McCann, M. Menegus, K. McCormick, M. Frampton, et al 1999. Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clin. Immunol. 90: 213-219. [Medline]




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