IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection.

TitleIL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection.
Publication TypeJournal Article
Year of Publication2009
AuthorsSereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, Battaglia CA, Landay AL, Pahwa S, Fischl MA, Asmuth DM, Tenorio AR, Altman JD, Fox L, Moir S, Malaspina A, Morre M, Buffet R, Silvestri G, Lederman MM
Corporate AuthorsACTG 5214 Study Team
JournalBlood
Volume113
Issue25
Pagination6304-14
Date Published2009 Jun 18
ISSN1528-0020
KeywordsAdult, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Cycle, Down-Regulation, Drug-Induced Liver Injury, Female, HIV Infections, HIV-1, Humans, Immunologic Memory, Interleukin-7, Interleukin-7 Receptor alpha Subunit, Lymphocyte Count, Male, Maximum Tolerated Dose, Middle Aged, Recombinant Proteins, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Viral Load
Abstract

Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes. The safety and activity of recombinant human IL-7 (rhIL-7) administration were therefore examined in HIV-infected persons. In this prospective randomized placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated with biologic activity demonstrable at 3 microg/kg and a maximum tolerated dose of 30 microg/kg. Injection site reactions and transient elevations of liver function tests were the most notable side effects. Transient increases in plasma HIV-RNA levels were observed in 6 of 11 IL-7-treated patients. Recombinant hIL-7 induced CD4 and CD8 T cells to enter cell cycle; cell-cycle entry was also confirmed in antigen-specific CD8 T cells. Administration of rhIL-7 led to transient down-regulation of the IL-7 receptor alpha chain (CD127) in both CD4(+) and CD8(+) T cells. Single-dose rhIL-7 increased the numbers of circulating CD4(+) and CD8(+) T cells, predominantly of central memory phenotype. The frequency of CD4(+) T cells with a regulatory T-cell phenotype (CD25(high) CD127(low)) did not change after rhIL-7 administration. Thus, rhIL-7 has a biologic and toxicity profile suggesting a potential for therapeutic trials in HIV infection and other settings of lymphopenia. This clinical trial has been registered at http://www.clinicaltrials.gov under NCT0099671.

DOI10.1182/blood-2008-10-186601
Alternate JournalBlood
PubMed ID19380868
PubMed Central IDPMC2710926
Grant ListAI 25879 / AI / NIAID NIH HHS / United States
AI 25915 / AI / NIAID NIH HHS / United States
AI 27675 / AI / NIAID NIH HHS / United States
AI 38855 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI 68636 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States