Effect of IL-7 therapy on naive and memory T cell homeostasis in aged rhesus macaques

Afam A. Okoye, Mukta Rohankhedkar, Audrie L. Konfe, Chike O. Abana, Matthew D. Reyes, Joseph A. Clock, Derick M. Duell, Andrew W. Sylwester, Partha Sammader, Alfred W. Legasse, Byung S. Park, Michael K. Axthelm, Janko Nikolich-Zugich, Louis J. Picker

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14 Scopus citations

Abstract

Aging is associated with gradual deterioration of adaptive immune function, a hallmark of which is the profound loss of naive T cells (TN) associated with decline in thymic output and export of new cells into the peripheral T cell pool. Because the lymphotropic cytokine IL-7 plays crucial roles in both development of TN in the thymus and TN homeostasis in the periphery, we sought to determine the extent to which therapeutic administration of IL-7 could reverse TN deficiency in aging rhesus macaques (RM), either by enhancement of the demonstrably reduced thymopoiesis or by peripheral TN expansion. Our results indicate that treatment of both adult (8-15 y) and old (>20 y) RM with recombinant simian IL-7 (rsIL-7) results in only transient increases in peripheral CD4+ and CD8+ TN numbers with no long-term benefit, even with repeated therapy. This transient effect was due to peripheral TN expansion and not enhanced thymic function, and appeared to be limited by induction of IL-7 nonresponsiveness. However, rsIL-7 therapy had a more promising effect on the central memory T cell (TCM) population (both CD4+ and CD8+) in adult and old RM, doubling the numbers of these cells in circulation and maintaining this larger population long term. IL-7 therapy did not reduce TCR diversity of the memory T cell compartment, suggesting that rsIL-7-induced expansion was symmetrical. Thus, although rsIL-7 failed to counter age-associated TN loss, the ability of this therapy to expand clonotypically diverse CD4+ and CD8+ TCM populations might potentially improve adaptive immune responsiveness in the elderly.

Original languageEnglish (US)
Pages (from-to)4292-4305
Number of pages14
JournalJournal of Immunology
Volume195
Issue number9
DOIs
StatePublished - Nov 1 2015

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ASJC Scopus subject areas

  • Immunology

Cite this

Okoye, A. A., Rohankhedkar, M., Konfe, A. L., Abana, C. O., Reyes, M. D., Clock, J. A., Duell, D. M., Sylwester, A. W., Sammader, P., Legasse, A. W., Park, B. S., Axthelm, M. K., Nikolich-Zugich, J., & Picker, L. J. (2015). Effect of IL-7 therapy on naive and memory T cell homeostasis in aged rhesus macaques. Journal of Immunology, 195(9), 4292-4305. https://doi.org/10.4049/jimmunol.1500609