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

Division of Immunology, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria

In a recent article, van Leeuwen et al. (1) analyze virus-specific and total CD8⁺ T cells from patients before and after renal transplantation. One of the authors’ major conclusions is that the expansion of CMV-specific CD8⁺ T cells after CMV infection leads to a long-lasting enlargement of the CD8⁺ T cell compartment, which would exclude the necessity of CMV-specific CD8⁺ T cells to compete for space with pre-existing memory T cells of other specificities (2). Van Leeuwen et al. claim that the human immune system is sufficiently flexible to expand when encountering CMV. We would like to point out that these general conclusions are made on the basis of data from transplant patients only, whereas we find that absolute CD8⁺ T cell numbers do not differ in healthy CMV-positive and CMV-negative individuals. Analyzing cohorts of CMV-seronegative (n = 24; age range, 26–84 years) and CMV-seropositive (n = 38; age range, 24–90 years) persons, we demonstrate slightly increased percentages of CD8⁺ T cells in CMV-positive donors (Fig. 1A) but no difference in absolute CD8⁺ T cell numbers (Fig. 1B). From this we conclude that the proposed concept that CMV infection leads to an enlargement of the CD8⁺ T cell compartment cannot be confirmed in healthy donors and that memory T cells of different specificities may still compete for space, as demonstrated in mice. Findings based on data obtained from immunosuppressed renal transplant recipients should thus be handled with great care to describe the situation in healthy individuals with latent CMV infection.

View larger version (6K): [in this window] [in a new window]   FIGURE 1. Absolute numbers of total CD8+ T cells are not affected by CMV seropositivity. PBMCs were isolated from a known volume of peripheral blood using density gradient centrifugation; absolute CD8+ T cell numbers were then obtained by gating CD3+CD8+ cells via flow cytometry technique. Percentages (A) and absolute numbers (B) of total CD8+ T cells are shown for CMV-seronegative and CMV-seropositive individuals. The median for each group is indicated; *, p < 0.05 (Mann-Whitney U test).

Acknowledgments

We are grateful to all members of the Immunology Division of the Institute for Biomedical Aging Research for providing their data of healthy donors with and without latent CMV infection.

References

1. van Leeuwen, E. M. M., J. J. Koning, E. B. M. Remmerswaal, D. van Baarle, R. A. W. van Lier, I. M. J. 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]
2. Khan, N., A. Hislop, N. Gudgeon, M. Cobbold, R. Khanna, L. Nayak, A. B. Rickinson, P. A. Moss. 2004. Herpesvirus-specific CD8 T cell immunity in old age: cytomegalovirus impairs the response to a coresident EBV infection. J. Immunol. 173: 7481-7489. [Abstract/Free Full Text]

This article has been cited by other articles:

				E. M. M. van Leeuwen, R. A. W. van Lier, and I. J. M. ten Berge Response to Comment on "Differential Usage of Cellular Niches by Cytomegalovirus versus EBV- and Influenza Virus-Specific CD8+ T Cells" J. Immunol., March 1, 2007; 178(5): 2612 - 2612. [Full Text] [PDF]

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