Association Between Telomere Length and Experimentally Induced Upper Respiratory Viral Infection in Healthy Adults

IMPORTANCE: Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations. OBJECTIVE: To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults. DESIGN, SETTING, AND PARTICIPANTS: Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness. MAIN OUTCOME MEASURES: Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness). RESULTS: Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio OR per 1-SD decrease in telomere length, 1.71 95% CI, 1.08-2.72; n = 128 shortest tertile 77% infected; middle, 66%; longest, 57%; CD4: OR, 1.76 95% CI, 1.15-2.70; n = 146 shortest tertile 80% infected; middle, 71%; longest, 54%; CD8CD28+: OR, 1.93 95% CI, 1.21-3.09, n = 132 shortest tertile 84% infected; middle, 64%; longest, 58%; CD8CD28-: OR, 2.02 95% CI, 1.29-3.16; n = 144 shortest tertile 77% infected; middle, 75%; longest, 50%). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 95% CI, 1.01-2.84; n = 144 shortest tertile, 26%; middle, 22%; longest, 13%). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 95% CI, 0.02-0.16, P = .01, n = 144). CONCLUSION AND RELEVANCE: In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.