IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells

Abstract

Lymphopenia is a serious consequence of HIV infection and the administration of cancer chemotherapeutic agents. Although growth factors can be administered to patients to increase circulating neutrophils, there is no effective method to stimulate CD8+ lymphocyte production in humans, in vivo. This report is the first to describe the administration of recombinant interleukin-7 to humans and demonstrates the ability of this cytokine to mediate selective increases in CD4+ and CD8+ lymphocytes along with a decrease in the percentage of CD4+ T-regulatory cells. These studies suggest an important role for interleukin-7 in the treatment of patients with lymphopenia.

FIGURE 1

Changes in circulating levels of hematopoietic cells in patients receiving IL-7. Each line represents an individual patient. A, Absolute neutrophil (filled symbols) and absolute lymphocyte (empty symbols) counts. B, CD4⁺ (filled symbols) and CD8⁺ (empty symbols) cells. C, CD4/CD8 ratio for each patient.

FIGURE 2

Peripheral blood mononuclear cells from 3 patients (60 λμg/kg dose) (A) were stained with fluorescein isothiocynate-conjugated CD4, PerCP-conjugated CD3, and APC-conjugated CD25 antibodies followed by intracellular staining with biotinylated Foxp3 antibody. The dot plots were gated on CD3⁺ T lymphocytes. B, Peripheral blood mononuclear cells from these patients were also stained with fluorescein isothiocynate-conjugated CD4, PE-conjugated CD25, and antigen presenting cells-conjugated CD127 (IL-7Rαchain) followed by intracellular staining for Foxp3 protein. The dot plots were gated on CD3⁺CD4⁺ T cells. The quadrants were set based on isotype control antibodies as well as negative control, and the numbers represent the percentage of cells in each quadrant.