IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy.
Despite efficient antiretroviral therapy (ART), CD4+ T cell counts often remain low in HIV-1-infected patients. This has led to IL-7, a crucial cytokine involved in both thymopoiesis and peripheral T cell homeostasis, being suggested as an additional therapeutic strategy. We investigated whether recombinant simian IL-7-treatment enhanced the T cell renewal initiated by ART in rhesus macaques chronically infected with SIVmac251. Six macaques in the early chronic phase of SIV infection received antiretroviral treatment. Four macaques also received a 3-wk course of IL-7 injections. Viral load was unaffected by IL-7 treatment. IL-7 treatment increased the number of circulating CD4+ and CD8+ memory T cells expressing activation (HLA-DR+, CD25+) and proliferation (Ki-67+) markers. It also increased naive (CD45RAbrightCD62L+) T cell counts by peripheral proliferation and enhanced de novo thymic production. The studied parameters returned to pretreatment values by day 29 after the initiation of treatment, concomitantly to the appearance of anti-IL-7 neutralizing Abs, supporting the need for a nonimmunogenic molecule for human treatment. Thus, IL-7, which increases T cell memory and de novo renewal of naive T cells may have additional benefits in HIV-infected patients receiving ART.
Beq
Stéphanie
S
Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France.
Nugeyre
Marie-Thérèse
MT
Ho Tsong Fang
Raphaël
R
Gautier
David
D
Legrand
Roger
R
Schmitt
Nathalie
N
Estaquier
Jérôme
J
Barré-Sinoussi
Françoise
F
Hurtrel
Bruno
B
Cheynier
Rémi
R
Israël
Nicole
N
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000235:genetics; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology
D000998:Antiviral Agents; D015851:Interleukin-7; D011994:Recombinant Proteins; D004247:DNA