Over-expression of CD8+ T-cell activation is associated with decreased CD4+ cells in patients seeking treatment of Alcohol Use Disorder

Sanvisens, Arantza; Martínez-Cáceres, Eva; Teniente, Aina; Tor, Jordi; Muga, Roberto

doi:10.1016/j.drugalcdep.2017.07.023

Cited by 8 publications

(9 citation statements)

References 43 publications

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“…The positive correlation found with alcohol and marijuana use, can indicate the overall contribution of these drugs to trigger an inflammatory response during the withdrawal period. Disruption in immune system homeostasis was already showed in alcohol use dependents, which exhibited an increase of activated CD8 + T cells compared to healthy subjects (54). Moreover, acute alcohol withdrawal was associated to increase the TNF-α levels which can evoke an inflammatory response (63).…”

Section: Discussionmentioning

confidence: 95%

“…For instance, elevated percentage of T CD4 + cells were observed in individuals with cocaine use (52, 53), corroborating our findings; however, other studies did not find such association (15). In addition, alcohol exposure was related to a decline in total T CD4 + cells (54).…”

Section: Discussionmentioning

confidence: 99%

“…Other studies have showed that cocaine exposure elevated the percentage of naïve T CD8 + and total T CD8 + cells and decreased the percentage of T CD8 + memory cells subpopulation (15, 53, 56). Alcohol exposure can also lead to overexpression of activated T CD8 + cells (54). Regarding NK cells, data remains inconsistent.…”

Section: Discussionmentioning

confidence: 99%

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Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets

et al. 2019

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Background: Cocaine is a psychostimulant drug with high addictive proprieties. Evidence suggests that cocaine use leads to critical changes in the immune system, with significant effects on T, B, and natural killer (NK) cells and influencing peripheral levels of cytokines. The presence of abstinence-related symptoms during detoxification treatment is known to influence the prognosis. Here, our aim was to investigate immune profiles in women with cocaine use disorder (CUD) according to withdrawal symptoms severity.Methods: Blood samples and clinical data were collected at onset of detoxification treatment of 50 women with CUD. The patients were stratified according to Cocaine Selective Severity Assessment (CSSA) scores in low withdrawal (L-W) and high withdrawal (H-W) categories. In addition, we also included a control group with 19 healthy women as reference to immune parameters. Peripheral blood was collected and lymphocyte subsets were phenotyped by multi-color flow cytometry (B cells, CD4+ T, CD8+ T, NK cells, and different stages of T-cell differentiation). PBMCs from patients and healthy controls were stimulated in vitro with phytohemagglutinin (1%) for 72 h to assess the production of Th1/Th2/Th17 cytokines.Results: Following stimulation, lymphocytes from women with CUD produced increased levels of Th1/Th2/Th17 cytokines. However, higher levels of IL-2 and IL-17 were observed only in the L-W group, while higher levels of IL-6 were detected in the H-W group compared to controls. H-W group showed lower percentage of early-differentiated Th cells (CD4+CD27+CD28+), elevated percentage of Th cells (CD3+CD4+), intermediate-differentiated Th cells (CD4+CD27−CD28+), and B cells (CD3−CD19+). Both CUD groups showed decreased percentages of naïve T cells (CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+).Conclusion: Our data demonstrated that CUD can lead to increased production of Th1/Th2/Th17 cytokines and lymphocyte changes.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets

et al. 2019

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“…The relative increase in NK cell population was related to a decrease in the proportion of T cells. CD4 + lymphopenia has been associated with the expression of markers of chronic activation in heavy drinkers [30] and with the expression of markers of immunosenescence in alcohol-related cirrhosis [31]. T cell lymphopenia is a common finding in patients with acute and chronic alcohol exposure [32], which may make patients susceptible to infections and may increase their morbidity [33].…”

Section: Discussionmentioning

confidence: 99%

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Teniente-Serra

Fuster

Quirant‐Sánchez

et al. 2022

JCM

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Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = −0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.

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“…Similarly, T cells of alcohol drinking humans (12,15,16) and mice (13,14) show increased activation and inflammatory cytokine release consistent with a host phenotype marked by chronic inflammation (7). T cell subsets show differential responses to chronic alcohol exposure, with studies demonstrating loss of CD4 + T cells (17,18) and overactivation of CD8 + T cells (18), as well as decreased numbers of regulatory T cells (T reg ) in the dermis (19). Investigators have also reported that alcohol exposure impairs murine T cell tissue extravasation in response to inflammatory stimuli (10,20), while in vivo (21) and in vitro (21, 22) human studies have shown alcohol-exposed T cells to undergo enhanced activation-induced cell death (23).…”

Section: Introductionmentioning

confidence: 99%

Impact of chronic alcohol exposure on conventional and regulatory murine T cell subsets

et al. 2023

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IntroductionChronic alcohol use poses significant negative consequences to public health and, among its many biologic effects, is associated with significant T cell dysregulation within the adaptive immune system that has yet to be fully characterized. Novel, automated strategies for high dimensional flow cytometric analysis of the immune system are rapidly improving researchers’ ability to detect and characterize rare cell types.MethodsUsing a murine model of chronic alcohol ingestion in conjunction with viSNE and CITRUS analysis tools, we performed a machine-driven, exploratory analysis comparing rare splenic subpopulations within the conventional CD4+, regulatory CD4+ and CD8+ T cell compartments between alcohol- and water-fed animals.ResultsWhile there were no differences in the absolute numbers of bulk CD3+ T cells, bulk CD4+ T cells, bulk CD8+ T cells, Foxp3- CD4+ conventional T cells (Tconv) or Foxp3+ CD4+ regulatory T cells (Treg), we identified populations of naïve Helios+ CD4+Tconv and naïve CD103+ CD8+ splenic T cells that were decreased in chronically alcohol exposed mice versus water-fed controls. In addition, we identified increased CD69+ Treg and decreased CD103+ effector regulatory T cell (eTreg) subsets in conjunction with increased frequency of a population that may represent a transitional phenotype between central regulatory T cell (cTreg) and eTreg.DiscussionThese data provide further resolution into the character of decreased naïve T cell populations known to be present in alcohol exposed mice, as well as describe alterations in effector regulatory T cell phenotypes associated with the pathogenesis of chronic alcohol-induced immune dysfunction.

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Over-expression of CD8+ T-cell activation is associated with decreased CD4+ cells in patients seeking treatment of Alcohol Use Disorder

Cited by 8 publications

References 43 publications

Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets

Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Impact of chronic alcohol exposure on conventional and regulatory murine T cell subsets

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