T-lymphocytes Expressing CC Chemokine Receptor-5 Are Increased in Frail Older Adults

Overview

Journal J Am Geriatr Soc

Specialty Geriatrics

Date 2008 Apr 4

PMID 18384587

Citations 36

Authors

Umberto De Fanis

George C Wang

Neal S Fedarko

Jeremy D Walston

Vincenzo Casolaro

Sean X Leng

Affiliations

Soon will be listed here.

Abstract

Objectives: To evaluate the frequencies of T-lymphocytes expressing CC chemokine receptor-5 (CCR5(+) T-cells) and their relationship with frailty in older adults.

Design: Case-control study with an age-, race-, and sex-matched design.

Setting: General Clinical Research Center.

Participants: Community-dwelling adults aged 72 and older from Baltimore, Maryland.

Methods: Frailty was determined using five validated criteria: weakness, slow walking speed, fatigue, low physical activity, and weight loss. Those meeting three or more of these five criteria were defined as frail and those with none as nonfrail. Complete blood counts were performed to obtain peripheral lymphocyte counts using an automated (Coulter) counter. Peripheral blood was collected for surface immunofluorescent staining of CCR5 and other T-cell markers.

Results: Twenty-six frail and matched nonfrail participants (mean age+/-standard deviation 83.8+/-5.3, range 72-94) completed the study. Frail participants had higher CCR5(+), CCR5(+)CD8(+), and CCR5(+)CD45RO(-) T-cell counts than matched nonfrail controls (349+/-160/mm(3) vs 194+/-168/mm(3), P=.02; 208+/-98/mm(3) vs 105+/-62/mm(3), P=.02; and 189+/-149/mm(3) vs 52+/-36/mm(3), P=.01; respectively). Furthermore, there was a trend toward graded increase in these T-cell counts across the frailty scores in frail participants (e.g., CCR5(+)CD8(+) counts of 123+/-52/mm(3), 248+/-115/mm(3), and 360+/-215/mm(3) for those with frailty scores of 3, 4, and 5, respectively).

Conclusion: These initial results suggest an expansion of the CCR5(+) T-cell subpopulation in frailty. They provide a basis for further characterization of CCR5(+) T-cells and their role in frailty, with potential therapeutic implications.

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References

Cosmi L, Annunziato F, Galli MIG , Maggi RME , Nagata K, Romagnani S . CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. Eur J Immunol. 2000; 30(10):2972-9. DOI: 10.1002/1521-4141(200010)30:10<2972::AID-IMMU2972>3.0.CO;2-#. View

Leng S, Xue Q, Tian J, Walston J, Fried L . Inflammation and frailty in older women. J Am Geriatr Soc. 2007; 55(6):864-71. DOI: 10.1111/j.1532-5415.2007.01186.x. View

Walston J, McBurnie M, Newman A, Tracy R, Kop W, Hirsch C . Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002; 162(20):2333-41. DOI: 10.1001/archinte.162.20.2333. View

Semba R, Margolick J, Leng S, Walston J, Ricks M, Fried L . T cell subsets and mortality in older community-dwelling women. Exp Gerontol. 2005; 40(1-2):81-7. DOI: 10.1016/j.exger.2004.09.006. View

Mueller A, Strange P . The chemokine receptor, CCR5. Int J Biochem Cell Biol. 2003; 36(1):35-8. DOI: 10.1016/s1357-2725(03)00172-9. View

Yung R, Mo R . Aging is associated with increased human T cell CC chemokine receptor gene expression. J Interferon Cytokine Res. 2003; 23(10):575-82. DOI: 10.1089/107999003322485071. View

Liu R, Paxton W, Choe S, Ceradini D, Martin S, Horuk R . Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996; 86(3):367-77. DOI: 10.1016/s0092-8674(00)80110-5. View

Leng S, Cappola A, Andersen R, Blackman M, Koenig K, Blair M . Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res. 2004; 16(2):153-7. DOI: 10.1007/BF03324545. View

Fatkenheuer G, Pozniak A, Johnson M, Plettenberg A, Staszewski S, Hoepelman A . Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med. 2005; 11(11):1170-2. DOI: 10.1038/nm1319. View

10.

Fried L, Hadley E, Walston J, Newman A, Newman A, Guralnik J . From bedside to bench: research agenda for frailty. Sci Aging Knowledge Environ. 2005; 2005(31):pe24. DOI: 10.1126/sageke.2005.31.pe24. View

11.

Fried L, Tangen C, Walston J, Newman A, Hirsch C, Gottdiener J . Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56(3):M146-56. DOI: 10.1093/gerona/56.3.m146. View

12.

Chen J, Mo R, Lescure P, Misek D, Hanash S, Rochford R . Aging is associated with increased T-cell chemokine expression in C57BL/6 mice. J Gerontol A Biol Sci Med Sci. 2003; 58(11):975-83. DOI: 10.1093/gerona/58.11.b975. View

13.

Charo I, Ransohoff R . The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006; 354(6):610-21. DOI: 10.1056/NEJMra052723. View

14.

Gerard C, Rollins B . Chemokines and disease. Nat Immunol. 2001; 2(2):108-15. DOI: 10.1038/84209. View

15.

Balistreri C, Caruso C, Grimaldi M, Listi F, Vasto S, Orlando V . CCR5 receptor: biologic and genetic implications in age-related diseases. Ann N Y Acad Sci. 2007; 1100:162-72. DOI: 10.1196/annals.1395.014. View

16.

Miller R . The aging immune system: primer and prospectus. Science. 1996; 273(5271):70-4. DOI: 10.1126/science.273.5271.70. View

17.

Locati M, Bonecchi R, Corsi M . Chemokines and their receptors: roles in specific clinical conditions and measurement in the clinical laboratory. Am J Clin Pathol. 2005; 123 Suppl:S82-95. PMC: 7149461. DOI: 10.1309/M6U4B8L6TNAK4G9L. View

18.

Leng S, Chaves P, Koenig K, Walston J . Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002; 50(7):1268-71. DOI: 10.1046/j.1532-5415.2002.50315.x. View

19.

Loetscher P, Uguccioni M, BORDOLI L, Baggiolini M, Moser B, Chizzolini C . CCR5 is characteristic of Th1 lymphocytes. Nature. 1998; 391(6665):344-5. DOI: 10.1038/34814. View

20.

Qin S, Rottman J, Myers P, Kassam N, Weinblatt M, Loetscher M . The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest. 1998; 101(4):746-54. PMC: 508621. DOI: 10.1172/JCI1422. View