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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2159-2167
IMMUNOBIOLOGY
Long-term effects of intermittent interleukin 2 therapy
in patients with HIV infection: characterization of a novel subset of
CD4+/CD25+ T cells
Irini Sereti,
Hector Martinez-Wilson,
Julia A. Metcalf,
Michael W. Baseler,
Claire W. Hallahan,
Barbara Hahn,
Richard L. Hengel,
Richard T. Davey,
Joseph A. Kovacs, and
H. Clifford Lane
From the National Institute of Allergy and Infectious
Diseases, National Institutes of Health (NIH), Bethesda, MD; Science
Applications International Corp, Frederick, NC; Georgetown University,
Washington DC; and the Critical Care Medicine Department, Clinical
Center, NIH, Bethesda, MD.
The long-term immunologic effects of intermittent interleukin 2 (IL-2) therapy were evaluated in a cross-sectional study by comparing 3 groups: HIV-seronegative volunteers, HIV-infected (HIV+)
patients receiving highly active antiretroviral therapy (HAART), and
HIV+ patients receiving HAART and intermittent IL-2.
Whole-blood immunophenotyping was performed to study expression of the
IL-2 receptor chains on T lymphocytes and natural killer cells and to
further characterize CD4+/CD25+ T cells.
Increased CD25 expression, especially in CD4+ T cells but
also in CD8+ T cells, without increases in expression of
the  and  chains of the IL-2 receptor was detected in the IL-2
group. Up to 79% of naive CD4+ T cells (median, 61%) from
patients in the IL-2 group expressed CD25, and the number of naive
CD4+/CD25+ T cells correlated positively with
both the total and naive CD4+ T-cell counts. A discrete
population of CD45 double intermediate RA+/RO+
CD4+ cells was also preferentially expanded in the IL-2
group, and the number of these cells strongly correlated with the total
CD4+ count. Despite increases in CD25 expression, T
lymphocytes from patients treated with IL-2 did not have increased
expression of early (CD69) or late (CD95) activation markers or
evidence of recent proliferation (Ki67). Both
CD4+/CD25+ and
CD4+/CD25 cells from IL-2-treated
HIV+ patients proliferated in response to mitogens,
specific antigens, and T-cell-receptor-mediated stimuli. Thus,
intermittent administration of IL-2 in HIV+ patients leads
to preferential expansion of a unique subset of CD4+ T
cells that may represent a critical population in T-cell homeostasis.
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