Published online before print September 26, 2008

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(Journal of Leukocyte Biology. 2009;85:34-43.)
© 2009 by Society for Leukocyte Biology

Chronic ethanol induces inhibition of antigen-specific CD8⁺ but not CD4⁺ immunodominant T cell responses following Listeria monocytogenes inoculation

Prajwal Gurung^*,, Betty M. Young^*, Ruth A. Coleman^*, Susan Wiechert^*, Lucas E. Turner^*, Nancy B. Ray^*,1, Thomas J. Waldschmidt^*,, Kevin L. Legge^*, and Robert T. Cook^*,2

^* Department of Pathology and
Interdisciplinary Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

² Correspondence: Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. E-mail: robert-cook{at}uiowa.edu

ABSTRACT

Chronic ethanol consumption results in immunodeficiency. Previous work with chronic ethanol-fed mice has shown reduced splenic weight and cellularity, including reduced numbers of CD8⁺ T cells. However, antigen-specific CD8⁺ and CD4⁺ T cell responses in chronic ethanol-fed mice have been studied relatively little. We have used an attenuated Listeria monocytogenes strain DPL 1942 (LM actA) to inoculate mice and subsequently used CD4⁺ and CD8⁺ immunodominant peptides of LM to measure the CD4⁺ and CD8⁺ T cell responses after chronic ethanol exposure. We found no major differences between control and ethanol-fed mice in the kinetics and persistence of antigen-specific CD4⁺ T cells in response to an immunodominant LM peptide, as measured by intracellular IFN- staining. In contrast to CD4⁺ responses, three methods of in vitro antigen presentation indicated that the primary response of CD8⁺ T cells to several different epitopes was reduced significantly in mice chronically fed ethanol. Antigen-specific CD8⁺ T cells were also reduced in chronic ethanol-fed mice during the contraction phase of the primary response, and memory cells evaluated at 29 and 60 days after inoculation were reduced significantly. BrdU proliferation assays showed that in vivo proliferation of CD8⁺ T cells was reduced in ethanol-fed mice, and IL-2-dependent in vitro proliferation of naive CD8⁺ T cells was also reduced. In conclusion, these results suggest that antigen-specific CD4⁺ T cell responses to LM are affected little by chronic ethanol consumption; however, antigen-specific CD8⁺ T cell responses are reduced significantly, as are in vivo and in vitro proliferation. The reduction of antigen-specific CD8⁺ T cells may contribute strongly to the immunodeficiency caused by ethanol abuse.

Key Words: CD8⁺ T cells • attenuated Listeria • actA • intracellular bacteria