Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets

Claude Sportes, Frances T. Hakim, Sarfraz A. Memon, Hua Zhang, Kevin S. Chua, Margaret R. Brown, Thomas A. Fleisher, Michael C. Krumlauf, Rebecca R. Babb, Catherine K. Chow, Terry J. Fry, Julie Engels, Renaud Buffet, Michel Morre, Robert J. Amato, David J. Venzon, Robert Korngold, Andrew Pecora, Ronald E. Gress, Crystal L. Mackall

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4+ and CD8+ T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects ' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8+ effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion.

Original languageEnglish (US)
Pages (from-to)1701-1714
Number of pages14
JournalJournal of Experimental Medicine
Volume205
Issue number7
DOIs
StatePublished - Jul 7 2008
Externally publishedYes

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Interleukin-7
T-Lymphocyte Subsets
T-Cell Antigen Receptor
T-Lymphocytes
Lymphocyte Depletion
Cytokines
Primates
Up-Regulation
Therapeutics
HIV
Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. / Sportes, Claude; Hakim, Frances T.; Memon, Sarfraz A.; Zhang, Hua; Chua, Kevin S.; Brown, Margaret R.; Fleisher, Thomas A.; Krumlauf, Michael C.; Babb, Rebecca R.; Chow, Catherine K.; Fry, Terry J.; Engels, Julie; Buffet, Renaud; Morre, Michel; Amato, Robert J.; Venzon, David J.; Korngold, Robert; Pecora, Andrew; Gress, Ronald E.; Mackall, Crystal L.

In: Journal of Experimental Medicine, Vol. 205, No. 7, 07.07.2008, p. 1701-1714.

Research output: Contribution to journalArticle

Sportes, C, Hakim, FT, Memon, SA, Zhang, H, Chua, KS, Brown, MR, Fleisher, TA, Krumlauf, MC, Babb, RR, Chow, CK, Fry, TJ, Engels, J, Buffet, R, Morre, M, Amato, RJ, Venzon, DJ, Korngold, R, Pecora, A, Gress, RE & Mackall, CL 2008, 'Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets', Journal of Experimental Medicine, vol. 205, no. 7, pp. 1701-1714. https://doi.org/10.1084/jem.20071681
Sportes, Claude ; Hakim, Frances T. ; Memon, Sarfraz A. ; Zhang, Hua ; Chua, Kevin S. ; Brown, Margaret R. ; Fleisher, Thomas A. ; Krumlauf, Michael C. ; Babb, Rebecca R. ; Chow, Catherine K. ; Fry, Terry J. ; Engels, Julie ; Buffet, Renaud ; Morre, Michel ; Amato, Robert J. ; Venzon, David J. ; Korngold, Robert ; Pecora, Andrew ; Gress, Ronald E. ; Mackall, Crystal L. / Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. In: Journal of Experimental Medicine. 2008 ; Vol. 205, No. 7. pp. 1701-1714.
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