Aging of the immune system (immune senescence) is accompanied by weakening of immune defense against a wide spectrum of pathogens, particularly those that have not been previously encountered by the host. This clinically correlates with increased morbidity and mortality from infectious diseases, which consistently rank in the top five causes of death amongst those 65 and older. T-cell alterations are amongst the most profound and most consistent changes observed in immune senescence. Age-related deficiencies in T-cell immunity are evident directly, in the form of impaired effector response to pathogens, or indirectly, in the form of increased and inflated memory T-cell pool at the expense of na?ve T- cells. Correction of T-cell immunity often rectifies symptoms of age-related immune senescence, and it is generally believed that reconstitution of na?ve T-cells, which are critical for defending us against at the wide spectrum of pathogens. Restoration of the na?ve T-cell numbers and function is therefore one of the key goals in combating immune aging. The principal goal of this application is to examine in non-human primates whether cytokines/growth factors IL-7 and/or KGF can increase na?ve T-cell production in the thymus and/or expand na?ve T cell pools in the periphery. As a corollary, na?ve T-cell rejuvenation will be tested functionally, by examining the ability of rejuvenating KGF/IL-7 treatment to improve the response of old monkeys to vaccination. Public Health Relevance Statement Elderly are the fastest growing segment of our society, and are inadequately protected against infectious diseases due to the aging of the immune system. Successful completion of these experiments would allow us to proceed with therapy of human immune aging with the ultimate goal to reduce, and eventually eliminate, excessive death and illness of the elderly from infectious diseases.

Public Health Relevance

Elderly are the fastest growing segment of our society, and are inadequately protected against infectious diseases due to the aging of the immune system. Successful completion of these experiments would allow us to proceed with therapy of human immune aging with the ultimate goal to reduce, and eventually eliminate, excessive death and illness of the elderly from infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI082529-04
Application #
8239573
Study Section
Special Emphasis Panel (ZAI1-BDP-I (J2))
Program Officer
Prabhudas, Mercy R
Project Start
2009-04-15
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$694,478
Indirect Cost
$200,477
Name
Oregon Health and Science University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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Nikolich-┼Żugich, Janko (2014) Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol 193:2622-9
Cicin-Sain, Luka; Sylwester, Andrew W; Hagen, Shoko I et al. (2011) Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques. J Immunol 187:1722-32