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.
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.
|DeGottardi, Maren Q; Okoye, Afam A; Vaidya, Mukta et al. (2016) Effect of Anti-IL-15 Administration on T Cell and NK Cell Homeostasis in Rhesus Macaques. J Immunol 197:1183-98|
|Okoye, Afam A; Rohankhedkar, Mukta; Konfe, Audrie L et al. (2015) Effect of IL-7 Therapy on Naive and Memory T Cell Homeostasis in Aged Rhesus Macaques. J Immunol 195:4292-305|
|Nikolich-Å½ugich, Janko (2014) Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol 193:2622-9|
|Renkema, Kristin R; Li, Gang; Wu, Angela et al. (2014) Two separate defects affecting true naive or virtual memory T cell precursors combine to reduce naive T cell responses with aging. J Immunol 192:151-9|
|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|