T-Cell Immunity Against Cytomegalovirus in Older Adults
Human cytomegalovirus (CMV) is a large DNA virus known to persist in some immunocompetent individuals after primary infection, establishing a chronic infection. Chronic CMV infection is highly prevalent by positive anti-CMV IgG serology in the general older adult population and in several chronic conditions including HIV infection. As discussed elsewhere in this handbook, a large number of studies have shown expansion of T cells specific to CMV pp65 or immediate early 1 (IE1) epitopes in some seropositive older adults, suggesting chronic CMV infection as a major driving force in T-cell immunosenescence with significant adverse impact on the health of older adults. However, most of these studies are cross-sectional, and CMV-seropositive older adult population is likely heterogeneous. This chapter will address this heterogeneity and provide supportive evidence for PCR-based assays to detect CMV viral DNA in the peripheral blood monocytes as novel tools for diagnostic evaluation of chronic CMV infection in older adults. It will also describe CD4+ and CD8+ T-cell responses to broad CMV epitopes beyond pp65 or IE1 emphasizing the importance of such comprehensive evaluation. Finally, it will present emerging longitudinal data for chronic CMV infection and its impact on T-cell immunity, emphasizing the need for more in-depth longitudinal studies with larger sample size, frequent sampling, and longer follow-up.
KeywordsCytomegalovirus T-cell immunity Aging Heterogeneity longitudinal
This work was supported in part by an NIH grant R01AI108907 and R21-AG-043874 and funding from the Milstein Medical Asian American Partnership (MMAAP) Foundation (www.mmaapf.org) [to Dr. Sean X. Leng], NIH grant UO1-AI-35042 [to Dr. Joseph B Margolick], and additional supplemental funding from the National Cancer Institute [to the MACS].
- Bajwa M, Vita S, Vescovini R, Larsen M, Sansoni P, Terrazzini N et al (2016) Functional diversity of cytomegalovirus-specific T cells is maintained in older people and significantly associated with protein specificity and response size. J Infect Dis 214(9):1430–1437CrossRefPubMedPubMedCentralGoogle Scholar
- Hadrup SR, Strindhall J, Kollgaard T, Seremet T, Johansson B, Pawelec G et al (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 176(4):2645–2653CrossRefPubMedGoogle Scholar
- Haq K, Fulop T, Tedder G, Gentleman B, Garneau H, Meneilly GS et al (2017) Cytomegalovirus seropositivity predicts a decline in the T cell but not the antibody response to influenza in vaccinated older adults independent of type 2 diabetes status. J Gerontol A Biol Sci Med Sci 72 (9):1163–70Google Scholar
- Li H, Weng P, Najarro K, Xue QL, Semba RD, Margolick JB et al (2014b) Chronic CMV infection in older women: longitudinal comparisons of CMV DNA in peripheral monocytes, anti-CMV IgG titers, serum IL-6 levels, and CMV pp65 (NLV)-specific CD8(+) T-cell frequencies with twelve year follow-up. Exp Gerontol 54:84–89CrossRefPubMedGoogle Scholar
- Mocarski E, Shenk T, Pass RF (2007) Cytomegalovirus. In: Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott, Williams & Wilkins, Philadelphia, pp 2701–2772Google Scholar
- Roberts ET, Haan MN, Dowd JB, Aiello AE (2010) Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol 172(4): 363–371Google Scholar
- Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Lofgren S et al (2006) The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev 127(8): 695–704CrossRefPubMedGoogle Scholar