Decreases in IL-7 levels during antiretroviral treatment of HIV infection suggest a primary mechanism of receptor-mediated clearance.

Abstract

IL-7 is essential for T-cell homeostasis. Elevated serum IL-7 levels in lymphopenic states, including HIV infection, are thought to be due to increased production by homeostatic feedback, decreased receptor-mediated clearance, or both. The goal of this study was to understand how immune reconstitution through antiretroviral therapy (ART) in HIV(+) patients affects IL-7 serum levels, expression of the IL-7 receptor (CD127), and T-cell cycling. Immunophenotypic analysis of T cells from 29 HIV(-) controls and 43 untreated HIV(+) patients (30 of whom were followed longitudinally for ≤ 24 months on ART) was performed. Restoration of both CD4(+) and CD8(+) T cells was driven by increases in CD127(+) naive and central memory T cells. CD4(+) T-cell subsets were not fully restored after 2 years of ART, whereas serum IL-7 levels normalized by 1 year of ART. Mathematical modeling indicated that changes in serum IL-7 levels could be accounted for by changes in the receptor concentration. These data suggest that T-cell restoration after ART in HIV infection is driven predominantly by CD127(+) cells and that decreases of serum IL-7 can be largely explained by improved CD127-mediated clearance.

• Authors: Jessica N Hodge, Sharat Srinivasula, Zonghui Hu, Sarah W Read, Brian O Porter, Insook Kim, Joann M Mican, Chang Paik, Paula Degrange, Michele Di Mascio, Irini Sereti
• Journal: Blood (Blood) Vol. 118 Issue 12 Pg. 3244-53 (Sep 22 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21778338 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Anti-Retroviral Agents
• Interleukin-7
• Receptors, Interleukin-7

Topics

• Adult
• Anti-Retroviral Agents (administration & dosage)
• Antiretroviral Therapy, Highly Active
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Case-Control Studies
• Female
• Flow Cytometry
• HIV Infections (blood, drug therapy, immunology, pathology, virology)
• HIV-1 (drug effects, immunology)
• Humans
• Immunophenotyping
• Interleukin-7 (blood, immunology)
• Longitudinal Studies
• Male
• Middle Aged
• Models, Theoretical
• Receptors, Interleukin-7 (biosynthesis, blood, immunology)
• T-Lymphocyte Subsets (immunology)
• Viral Load (drug effects)