title: Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia.
abstract: Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/µL) 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 dose-escalation 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 and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Virginia
authors.identifier: http://orcid.org/0000-0003-2006-7440
authors.initials: V
authors.lastname: Sheikh
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Brian O
authors.initials: BO
authors.lastname: Porter
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Rebecca
authors.initials: R
authors.lastname: DerSimonian
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD;
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kovacs
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: William L
authors.initials: WL
authors.lastname: Thompson
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Perez-Diez
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Gregg
authors.initials: G
authors.lastname: Roby
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: JoAnn
authors.initials: J
authors.lastname: Mican
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Alice
authors.initials: A
authors.lastname: Pau
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD;
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD;
authors.forename: Joseph
authors.initials: J
authors.lastname: Adelsberger
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD;
authors.forename: Jeanette
authors.initials: J
authors.lastname: Higgins
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Bourgeois
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Stig M R
authors.initials: SM
authors.lastname: Jensen
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD;
authors.forename: David R
authors.initials: DR
authors.lastname: Morcock
authors.affiliation: Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD;
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burbelo
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Leah
authors.initials: L
authors.lastname: Osnos
authors.affiliation: Hematology Section, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, MD; and.
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.affiliation: Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD;
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.affiliation: Cytheris Inc., Subsidiary of Cytheris S.A., Issy les Moulineaux, France.
authors.forename: Therese
authors.initials: T
authors.lastname: Croughs
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Michael D
authors.initials: MD
authors.lastname: Yao
authors.affiliation: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD;
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD;
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D015851:Interleukin-7; D011994:Recombinant Proteins