IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates

Terry J. Fry, Marcin Moniuszko, Stephen Creekmore, Susan J. Donohue, Daniel C. Douek, Steven Giardina, Toby T. Hecht, Brenna J. Hill, Kristen Komschlies, Joseph Tomaszewski, Genoveffa Franchini, Crystal L. Mackall

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-7 (IL-7) is important for thymopoiesis in mice and humans because IL-7 receptor α (IL-7Rα) mutations result in a severe combined immunodeficiency phenotype with severe thymic hypoplasia. Recent evidence has indicated that IL-7 also plays an important role as a regulator of T-cell homeostasis. Here we report the immunologic effects of recombinant human IL-7 (rhIL-7) therapy in normal and simian immunodeficiency virus (SIV)-infected nonhuman primates. Cynomolgus monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4+ and CD8+ subsets. Although IL-7 is known to have thymopoietic effects in mice, we observed marked declines in the frequency and absolute number of T-cell receptor excision circle-positive (TREC+) cells in the peripheral blood and dramatic increases in the percentage of cycling T cells in the peripheral blood as measured by Ki-67 expression (baseline less than 5% to approximately 50% after 6 days of therapy) and ex vivo bromodeoxyuridine (BrdU) incorporation. Similarly, moderately CD4-depleted SIV-infected macaques treated with rhIL-7 also had significant increases in peripheral blood CD4+ and CD8+ T cells following rhIL-7 therapy. Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination.

Original languageEnglish (US)
Pages (from-to)2294-2299
Number of pages6
JournalBlood
Volume101
Issue number6
DOIs
StatePublished - Mar 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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