T cell subsets and mortality in older community-dwelling women Richard D. Semba a,b,1, * , Joseph B. Margolick c , Sean Leng b , Jeremy Walston b , Michelle O. Ricks a , Linda P. Fried b a Division of Ocular Immunology, Department of Ophthalmology, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 700, Baltimore, MD 21287, USA b Center on Aging and Health, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 700, Baltimore, MD 21287, USA c Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 700, Baltimore, MD 21287, USA Received 16 March 2004; received in revised form 12 August 2004; accepted 16 September 2004 Available online 18 October 2004 Abstract The relationship between specific T cell subset alterations and mortality has not been well characterized in older adults. The specific aim was to determine whether specific T cell subsets are associated with an increased risk of death. We conducted a case-control study of T cell subsets (CD4 C and CD8 C T cells, and subsets of these cells defined by expression or non-expression of CD28, CD45RA, and CD45RO) nested within two complementary prospective cohorts of women aged 65 and over living in the community, the Women’s Health and Aging Studies (WHAS). Cases consisted of 61 women who died during 5 years of follow-up, and controls consisted of 61 women matched by age, frailty, and morbidities who survived during 7 years of follow-up. There were no significant differences between cases and controls in any of the T cell subsets studied. When analyses were stratified by frailty status, these data suggest that CD8 C CD28 K lymphocyte counts were significantly higher among women who were frail compared with pre-frail and non-frail women. q 2004 Published by Elsevier Inc. Keywords: Aging; CD4; CD8; CD28; CD45RA; CD45RO; T cell; Mortality; Women 1. Introduction Older age is associated with a decline of immunity, or immune senescence, and consequences of this impaired immunity may include vaccine failure (Webster, 2000), severe infections (Miller, 1996), and increased mortality (Roberts-Thomson et al., 1974). Aging is associated with alterations in T cell subsets, including reduced CD4/CD8 ratios (Mazari and Lesourd, 1998; Wikby et al., 1998; Fahey et al., 2000), reduced CD45RA C , or so-called naive T lymphocytes, and increased CD45RO C , or so-called memory lymphocytes (Gabriel et al., 1989; Utsuyama et al., 1992; Fahey et al., 2000), increased CD4 C CD8 C lymphocytes (Laux et al., 2000), and increased CD8 C CD28 K lymphocytes (Boucher et al., 1998; Fahey et al., 2000). A combination of high CD8 C and low CD4 C percen- tages and poor lymphocyte proliferation responses was associated with higher mortality in studies of older adults in Sweden (Ferguson et al., 1995; Wikby et al., 1998; Olsson et al., 2000). The age-related decrease in CD4 C lymphocyte counts is also associated with poorer nutritional status in older adults (Mazari and Lesourd, 1998). An increase in CD45RO C and decrease in CD45RA C may occur inde- pendently of health and nutritional status (Mazari and Lesourd, 1998), but another report suggested that the decrease in CD45RA C lymphocytes may be less pro- nounced in healthy centenarians than in younger healthy individuals (Cossarizza et al., 1996). Changes in CD45RA C and CD45RO C do not appear to be associated with adverse consequences such as vaccine failure (Goronzy et al., 2001), and the relationship between CD45RA C and CD45RO C 0531-5565/$ - see front matter q 2004 Published by Elsevier Inc. doi:10.1016/j.exger.2004.09.006 Experimental Gerontology 40 (2005) 81–87 www.elsevier.com/locate/expgero * Corresponding author. Tel.: C1 410 955 3572; fax: C1 410 955 0629. E-mail address: rdsemba@jhmi.edu (R.D. Semba). 1 Present address. Division of Ocular Immunology, Department of Ophthalmology, Center on Aging and Health, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 700, Baltimore, MD 21205, USA.