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(Journal of Leukocyte Biology. 2002;72:1109-1116.)
© 2002 by Society for Leukocyte Biology

Chronic ethanol consumption by mice results in activated splenic T cells

Kejing Song^*, Ruth A. Coleman^*, Xiaoyan Zhu^*,, Carol Alber, Zuhair K. Ballas^,, Thomas J. Waldschmidt^* and Robert T. Cook^*,

Departments of
^* Pathology
Internal Medicine, and
Surgery, College of Medicine, University of Iowa, Iowa City; and
Department of Veterans Affairs Medical Center, Iowa City, Iowa

Correspondence: Robert T. Cook, M.D., Ph.D., Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242. E-mail: robert-cook{at}uiowa.edu

Previous studies have shown that T cells from human alcoholics overexpress activation or memory markers such as human leukocyte antigen-DR, CD45RO, CD57, and CD11b and may have reduced levels of CD62L. In those studies, we demonstrated that the increased CD57⁺ T cell population rapidly produces interferon- (IFN-) and tumor necrosis factor , independent of a second signal requirement, consistent with an increased effector T cell population. In contrast to the length of alcohol abuse by human alcoholics, most work with mice has involved 2-week ethanol exposures or less, which result in decreased IFN- responses. In the present work, we have evaluated C57Bl/6 or BALB/c mice, which were administered 20% w/v ethanol in water for 3–13 weeks. In these mice, rapid cytoplasmic IFN- expression by T cells after stimulation through the T cell receptor was significantly increased versus normals. Studies of surface-activation markers showed that T cells from chronically ethanol-fed mice had reduced CD62L expression and an increased percentage of CD44^hi T cells. The CD44^hi subset was largely second signal-independent for secreted IFN- and interleukin (IL)-4 production at early times after stimulation. The enriched T cells of chronic ethanol mice secreted more IFN- and IL-4 than controls and equivalent IL-2 at early times after stimulation (6–24 h). The overall results support the concept that in humans and mice, chronic alcohol exposure of sufficient duration results in T cell activation or sensitization in vivo and an increased percentage of the effector/memory subset.

Key Words: alcohol • effector T cells • CD44^hi T cells • interferon- • IL-4

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