Chronic ethanol consumption by mice results in activated splenic T cells.
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-gamma (IFN-gamma) and tumor necrosis factor alpha, 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-gamma 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-gamma 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-gamma and interleukin (IL)-4 production at early times after stimulation. The enriched T cells of chronic ethanol mice secreted more IFN-gamma 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.
Song
Kejing
K
Department of Pathology, College of Medicine, University of Iowa, Iowa City 52242, USA.
Coleman
Ruth A
RA
Zhu
Xiaoyan
X
Alber
Carol
C
Ballas
Zuhair K
ZK
Waldschmidt
Thomas J
TJ
Cook
Robert T
RT
D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D018960:Hyaluronan Receptors; D007376:Interleukin-2; D019041:L-Selectin; D000431:Ethanol; D007371:Interferon-gamma