T_H1 cytokine response of CD57⁺ T-cell subsets in healthy controls and patients with alcoholic liver disease☆

Abstract 

Patients with chronic inflammatory diseases, including Crohn's disease and rheumatoid arthritis, as well as those with certain viral infections, and patients who are transplant recipients or who have certain hematologic malignancies have been observed to have CD57⁺ T cell expansion in both CD4⁺ and CD8⁺ subsets. We have reported previously that alcoholic patients also have CD57⁺ T cell expansion. Because many alcoholics become seriously deficient in cell-mediated immunity, it is of interest to determine whether the expanded CD57⁺ subsets can respond to stimulation with normal T helper cell subtype 1 (T_H1) cytokine production. We report evaluation of the CD57 T-cell subsets of patients with alcoholic liver disease (ALD) with the use of cytoplasmic staining after stimulation through the T-cell receptor (TCR). The CD57⁺ subsets of the T cells of both healthy individuals and patients with ALD express significantly higher amounts of cytoplasmic tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) after 6 h of stimulation than do the CD57⁻ subsets. This increased production can persist up to 46 h of continuous stimulation. Under these assay conditions, very little cytoplasmic interleukin (IL)-4 is observed in the T cells of either healthy control subjects or patients with ALD. Measurement of cytokine secretion by sort-purified CD57 T-cell subsets with the use of enzyme-linked immunosorbent assay (ELISA) shows that the CD57⁺ T-cell subset produces 18- to 30-fold more TNF-α and IFN-γ, respectively, than does the CD57⁻ subset in the first 12 h of stimulation. This response requires only stimulation through the TCR for the CD57⁺ subset, whereas significant secretion by the CD57⁻ subset requires added IL-2 or anti-CD28 antibody. These results are consistent with the concept of the CD57⁺ T-cell subset as a differentiated effector cell and demonstrate that patients with ALD who are not drinking at the time of evaluation have normal or increased immediate T_H1 T-cell responses.

Keywords:  CD57⁺ T cells, Cytokines, T_H1, Alcoholic