CD4+ T Cell Responses to Interleukin‐2 Administration in HIV‐Infected Patients Are Directly Related to the Baseline Level of Immune Activation
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
Background.
Intermittent interleukin (IL)–2 administration to human immunodeficiency virus (HIV)–infected patients leads to CD4+ T cell expansions. The factors potentially affecting these expansions were investigated in the present study.
Methods.A matched (for baseline CD4+ T cell count) case‐control study was designed. Nonresponders (NRs) were defined as patients with a 
10% increase in CD4+ T cell count 2 months after the third IL‐2 cycle (week 24), compared with that at baseline (week 0). Control subjects experienced a 
50% increase in CD4+ T cell count at week 24. Immunophenotype, Ki67 and forkhead box protein P3 (FoxP3) expression, and T cell receptor excision circle (TREC) measurements in T cells were evaluated at weeks 0 and 24 in both groups.
Results.Control subjects and NRs did not differ significantly at baseline in age, viral load, CD4+ T cell count, nadir CD4+ T cell count, or CD8+ T cell count. At week 0, NRs had lower TREC levels per 
T cells and higher levels of T cell proliferation and activation than did control subjects. At week 24, both groups experienced decreases in T cell proliferation and increases in CD25 and FoxP3 expression on CD4+ T cells, with TREC levels per 
CD4+ T cells decreasing significantly only in control subjects.
Conclusions.Increased immune activation can adversely affect CD4+ T cell expansions after IL‐2 administration. Despite the lack of expansion, other evidence of IL‐2–induced biological activity was observed.
Received 4 December 2006; accepted 26 March 2007; electronically published 16 July 2007.
Cited by
Online publication date: 1-Aug-2009.
CrossRef
Online publication date: 15-Jul-2009.
Online publication date: 15-Sep-2008.
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Potential conflicts of interest: The US Government has been granted a use patent for intermittent interleukin‐2 immunotherapy that includes J.A.K. and H.C.L. as coinventors. All other authors report no conflicts of interest.
Financial support: Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the Clinical Center, National Institutes of Health.
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Present affiliations: Drexel University College of Medicine, Philadelphia, Pennsylvania (P.S. and M.S.R.); Science Applications International Corporation, Frederick, Maryland (J.A.K. and H.C.L.).