Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

Virginia Sheikh, Brian O. Porter, Rebecca DerSimonian, Stephen B. Kovacs, William L. Thompson, Ainhoa Perez-Diez, Alexandra F. Freeman, Gregg Roby, Joann Mican, Alice Pau, Adam Rupert, Joseph Adelsberger, Jeanette Higgins, Jeffrey S. Bourgeois, Stig M.R. Jensen, David R. Morcock, Peter D. Burbelo, Leah Osnos, Irina Maric, Ven NatarajanTherese Croughs, Michael D. Yao, Jacob D. Estes, Irini Sereti

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/mL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A doseescalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses andmay represent a promising therapeutic intervention in ICL.

Original languageEnglish (US)
Pages (from-to)977-988
Number of pages12
JournalBlood
Volume127
Issue number8
DOIs
StatePublished - Feb 25 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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