Herpesvirus-Specific CD8 T Cell Immunity in Old Age: Cytomegalovirus Impairs the Response to a Coresident EBV Infection

Journal of Immunology - Tập 173 Số 12 - Trang 7481-7489 - 2004
Naeem Khan1, Andrew D. Hislop1, Nancy Gudgeon1, Mark Cobbold1, Rajiv Khanna2, Laxman Nayak3, Alan B. Rickinson1, Paul Moss1
1*CR U.K. Institute for Cancer Studies, Vincent Drive, Edgbaston, University of Birmingham, Birmingham, United Kingdom;
2† Division of Infectious Diseases and Immunology Queensland Institute of Medical Research, Herston, Queensland, Australia; and
3‡ Department of Applied Gerontology, Selly Oak, Birmingham, United Kingdom

Tóm tắt

Abstract Aging in humans is associated with increased infections and the reduced proliferative capacity of T cells, part of the more global phenomenon termed immune senescence. The etiology of immune senescence is unknown but the accumulation of virus-specific memory T cells may be a contributory factor. We have examined CD8 T cell responses to two persistent herpesvirus infections, CMV and EBV, and to a recurrent virus infection, influenza, in different age cohorts of healthy donors using HLA-peptide tetramers and intracellular cytokine detection. Of these, CMV appears to be the most immunogenic, with the CD8 T cell response representing over 10% of the CD8 pool in many elderly donors. Interestingly, the effect of age upon EBV-specific responses depends upon donor CMV sero-status. In CMV seropositive donors, the magnitude of the EBV-specific immune response is stable with age, but in CMV seronegative donors, the response to EBV increases significantly with age. By contrast, the influenza-specific CD8 T cell immune response decreases with age, independent of CMV status. The functional activity of the herpesvirus-specific immune response decreases in elderly donors, although the characteristic phenotypes of CMV- and EBV-specific memory populations are retained. This demonstrates that aging is associated with a marked accumulation of CMV-specific CD8 T cells together with a decrease in immediate effector function. Moreover, infection with CMV can reduce prevailing levels of immunity to EBV, another persistent virus. These results suggest that carriage of CMV may be detrimental to the immunocompetent host by suppressing heterologous virus-specific immunity during aging.

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Journal of Immunology

Tập 173 Số 12

7481-7489

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