Chronic alcohol consumption in mice increases the proportion of peripheral memory T cells by homeostatic proliferation

Abstract

This study examined the mechanism underlying the increase of peripheral memory phenotype T cells that occurs during chronic alcohol consumption in mice. Female C57BL/6 mice were given 20% (w/v) alcohol in the drinking water for 2 weeks to 6 months. Chronic alcohol consumption significantly induced peripheral T cell lymphopenia; up-regulated expression of CD44 on T cells and increased the percentage of CD4+CD44int/hi and CD8+CD44int/hi Ly6C+ T cells; up-regulated the expression of CD43 on CD8+ T cells; increased the percentage of interferon--producing T cells; decreased the percentage of CD8+CD28+ T cells; and down-regulated the expression of CD28 on CD4+ T cells. Expression of CD25 and CD69 on peripheral CD8+ T cells was not affected and inconsistently expressed on CD4+ T cells. Neither cell type showed altered expression of CD137 or CD153. Alcohol withdrawal did not abrogate the increase in CD8+Ly6C+cells induced by alcohol consumption. In vivo bromodeoxyuridine incorporation experiments demonstrated that chronic alcohol consumption decreases naïve T cells that are presumed to have emigrated from the thymus and increases proliferation of memory T cells, but accelerates peripheral T cell turnover. Together these results indicate that chronic alcohol consumption results in T cell lymphopenia, which in turn induces T cell homeostatic proliferation that increases the proportion of peripheral memory T cells relative to naïve T cells.

Ethanol prevents development of destructive arthritis

“…Chronic ethanol consumption is linked to a number of abnormalities of the immune system, including lymphopenia, and downregulation of certain costimulatory molecules on the T cell surface (20), as well as to decreased interaction between leukocytes and endothelial cells (21). Chronic ethanol abuse will typically lead to severe medical consequences, but the potential of beneficial consequences of moderate alcohol intake have been discussed for decades, e.g., with respect to the epidemiology of cardiovascular diseases (22)(23)(24)(25).…”

Chronic alcohol consumption inhibits melanoma growth but decreases the survival of mice immunized with tumor cell lysate and boosted with α-galactosylceramide

“…It is well known that chronic alcohol consumption affects the immune system [20]. A large body of data indicates that chronic alcohol consumption in humans and mice activates the immune system, which is reflected in the activation of CD8 + T cells, dendritic cells (DC), and NKT cells, and increased production of pro-inflammatory cytokines such as IFN-γ and TNF-α [21-25]. We found that chronic alcohol consumption along with advancing growth of s.c. melanoma leads to inhibition in the expansion of memory and melanoma-specific CD8 + T cells, acceleration in the decay of Th1 cytokine producing CD8 + T cells [26], and compromised circulation of mature B cells [27].…”

Alcohol Consumption and Antitumor Immunity: Dynamic Changes from Activation to Accelerated Deterioration of the Immune System

“…We and others found that chronic alcohol consumption in the steady state increases the percentage of CD8 + T cells exhibiting the memory phenotype and also CD8 + T cells producing IFN-γ [ 31 , 33 ]. We further showed that chronic alcohol consumption increases memory T cells in the steady state through the induction of T cell homeostatic proliferation [ 33 ]. These increased memory and IFN-γ-producing CD8 + T cells in alcohol-consuming mice could play an important protective role in the antitumor immune response.…”

“…The second is an antitumor function through presentation of antigen to T cells to enhance T cell activation and cytokine production. We found that in the steady state chronic alcohol consumption does not signifi cantly affect the B cell phenotype and nor their distribution in blood and lymph nodes; however, B cell numbers decrease in the spleen [ 33 ]. In melanoma-bearing mice B cells decrease around fourfold in the blood of alcoholconsuming mice with prolonged tumor growth compared to their water-drinking counterparts [ 70 ].…”