Impact of Immunonutrition on T Cell Activation: A Randomized Control Study in Cardiac Surgery Patients

Background. Cardiac surgery provokes an intense inflammatory response that can cause an immunosuppressive state and adverse postoperative outcomes. We recently showed that postoperative immunonutrition with glutamine in “fragile” low-risk cardiac surgery patients was associated with a significantly increased level of CD3+ and CD4+ T cells. In order to clarify the biological relevance and clinical importance of these findings, we investigated whether an increase in the CD4+ T cell level was caused by changes in the systemic inflammatory response (caused by surgery or infection) and if it was associated with their activation status.Methods. A randomized control study of low operative risk but “fragile” cardiac surgery patients was performed. Patients were randomized into immunonutrition (IN) and control groups (C). The IN group received normal daily meals plus special immune nutrients for 5 days postoperatively, while the C group received only normal daily meals. Laboratory parameters were investigated before surgery and on the sixth postoperative day and the groups were compared accordingly. The expression of the CD69+ marker was investigated to determine T cell activation status. Serum concentrations of cytokines (interleukin-10 (IL-10), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and C-reactive protein (CRP) were determined to assess the systemic inflammatory response, while procalcitonin (PCT) levels were evaluated to confirm or deny possible bacterial infection.Results. Fifty-five patients were enrolled in the study. Twenty-seven (49.1%) were randomized in the IN group. Results show that on the sixth postoperative day, the CD4+CD69+ and CD8+CD69+ counts did not differ between the IN and C groups, accordingly 0.25 [0.16–0.50] vs 0.22 [0.13-0.41], p=0.578 and 0.13 [0.06–0.3] vs 0.09 [0.05–0.14], p=0.178. Also, statistically significant differences were not observed in the cytokine levels (IN and C groups: TNF-α 8.13 [7.32–10.31] vs 8.78 [7.65–11.2], p=0.300; IL-6 14.65 [9.28–18.95] vs 12.25 [8.55–22.50], p=0.786; IL-10 5.0 [5.0–5.0] vs 5.0 [5.0–5.0], p=0.343 respectively), which imply that an elevated T cell count is not associated with the systemic inflammatory response. Also, PCT (IN and C groups: 0.03 [0.01–0.09] vs 0.05 [0.03–0.08], p=0.352) and CRP (IN and C groups 62.7 [34.2–106.0] vs 63.7 [32.9–91.0], p=0.840) levels did not differ between the two groups. Moreover, low levels of PCT indicated that the increase in T cell count was not determined by bacterial infection.Conclusions. Our findings showed that CD4+ T cell levels were associated with neither the systemic inflammatory response nor bacterial infection. Secondly, increases in T cells are not accompanied by their activation status. These results suggest a hypothesis that a higher postoperative T cell concentration may be associated with postoperative immunonutrition in low-risk cardiac surgery patients with intact cellular vitality, i.e. “fragile”. However, immunonutrition alone did not affect T cell activation status.

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CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance

Journal of Gastroenterology ◽

10.1007/s00535-021-01799-8 ◽

2021 ◽

Author(s):

Yan Yan ◽

Wei Zhao ◽

Wei Liu ◽

Yan Li ◽

Xu Wang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Crucial Role ◽

Cell Activation ◽

Hbv Infection ◽

Host Immune System ◽

Tnf Α ◽

Ifn Γ ◽

High Level

Abstract Background Chemokine (C–C motif) ligand 19 (CCL19) is a leukocyte chemoattractant that plays a crucial role in cell trafficking and leukocyte activation. Dysfunctional CD8+ T cells play a crucial role in persistent HBV infection. However, whether HBV can be cleared by CCL19-activated immunity remains unclear. Methods We assessed the effects of CCL19 on the activation of PBMCs in patients with HBV infection. We also examined how CCL19 influences HBV clearance and modulates HBV-responsive T cells in a mouse model of chronic hepatitis B (CHB). In addition, C–C chemokine-receptor type 7 (CCR7) knockdown mice were used to elucidate the underlying mechanism of CCL19/CCR7 axis-induced immune activation. Results From in vitro experiments, we found that CCL19 enhanced the frequencies of Ag-responsive IFN-γ+ CD8+ T cells from patients by approximately twofold, while CCR7 knockdown (LV-shCCR7) and LY294002 partially suppressed IFN-γ secretion. In mice, CCL19 overexpression led to rapid clearance of intrahepatic HBV likely through increased intrahepatic CD8+ T-cell proportion, decreased frequency of PD-1+ CD8+ T cells in blood and compromised suppression of hepatic APCs, with lymphocytes producing a significantly high level of Ag-responsive TNF-α and IFN-γ from CD8+ T cells. In both CCL19 over expressing and CCR7 knockdown (AAV-shCCR7) CHB mice, the frequency of CD8+ T-cell activation-induced cell death (AICD) increased, and a high level of Ag-responsive TNF-α and low levels of CD8+ regulatory T (Treg) cells were observed. Conclusions Findings in this study provide insights into how CCL19/CCR7 axis modulates the host immune system, which may promote the development of immunotherapeutic strategies for HBV treatment by overcoming T-cell tolerance.

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Changes in Inflammation but Not in T-Cell Activation Precede Non-AIDS-Defining Events in a Case-Control Study of Patients on Long-term Antiretroviral Therapy

The Journal of Infectious Diseases ◽

10.1093/infdis/jix666 ◽

2017 ◽

Vol 218 (2) ◽

pp. 239-248 ◽

Cited By ~ 11

Author(s):

Konstantia Angelidou ◽

Peter W Hunt ◽

Alan L Landay ◽

Cara C Wilson ◽

Benigno Rodriguez ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

T Cell Activation ◽

Cell Activation ◽

Case Control Study ◽

Case Control ◽

Control Study

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Akt Fine-tunes NF-κB-dependent Gene Expression during T Cell Activation

Journal of Biological Chemistry ◽

10.1074/jbc.m111.259549 ◽

2011 ◽

Vol 286 (41) ◽

pp. 36076-36085 ◽

Cited By ~ 37

Author(s):

Jing Cheng ◽

Binh Phong ◽

David C. Wilson ◽

Raphael Hirsch ◽

Lawrence P. Kane

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Gene Profiling ◽

Leukocyte Activation ◽

Mrna Transcription ◽

Tnf Α ◽

Fine Tune

Activation of the NF-κB signaling pathway is critical for leukocyte activation and development. Although previous studies suggested a role for the Akt kinase in coupling the T cell antigen receptor and CD28 to NF-κB activation in T cells, the nature of the role of Akt in this pathway is still unclear. Using a targeted gene profiling approach, we found that a subset of NF-κB-dependent genes required Akt for optimal up-regulation during T cell activation. The selective effects of Akt were manifest at the level of mRNA transcription and p65/RelA binding to upstream promoters and appear to be due to altered formation of the Carma1-Bcl10 complex. The proinflammatory cytokine TNF-α was found to be particularly sensitive to Akt inhibition or knockdown, including in primary human blood T cells and a murine model of rheumatoid arthritis. Our findings are consistent with a hierarchy in the expression of NF-κB-dependent genes, controlled by the strength and/or duration of NF-κB signaling. More broadly, our results suggest that defining the more graded effects of signaling, such as those demonstrated here for Akt and the NF-κB pathway, is important to understanding how cells can fine-tune signaling responses for optimal sensitivity and specificity.

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Abnormal Helper-Inducer/Suppressor-Inducer T-Cell Subset Distribution and T-Cell Activation Status are Common to All Types of Chronic Synovitis

Scandinavian Journal of Immunology ◽

10.1111/j.1365-3083.1988.tb02435.x ◽

1988 ◽

Vol 28 (2) ◽

pp. 225-232 ◽

Cited By ~ 35

Author(s):

G. KINGSLEY ◽

C. PITZALIS ◽

N. KYRIAZIS ◽

G. S. PANAYI

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cell Subset ◽

T Cell Subset ◽

Chronic Synovitis ◽

Subset Distribution ◽

Activation Status

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The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis

Journal of Experimental Medicine ◽

10.1084/jem.20031064 ◽

2004 ◽

Vol 199 (2) ◽

pp. 185-197 ◽

Cited By ~ 131

Author(s):

Naoto Kawakami ◽

Silke Lassmann ◽

Zhaoxia Li ◽

Francesca Odoardi ◽

Thomas Ritter ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Inflammatory Response ◽

T Cell Activation ◽

Cell Activation ◽

Expression Patterns ◽

Target Tissue ◽

Autoimmune Encephalomyelitis ◽

Effector T Cell ◽

Green Fluorescent

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

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Differential CD147 Functional Epitopes on Distinct Leukocyte Subsets

Frontiers in Immunology ◽

10.3389/fimmu.2021.704309 ◽

2021 ◽

Vol 12 ◽

Author(s):

Supansa Pata ◽

Sirirat Surinkaew ◽

Nuchjira Takheaw ◽

Witida Laopajon ◽

Kantinan Chuensirikulchai ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cell Function ◽

Inflammatory Diseases ◽

Cell Contact ◽

Cell Functions ◽

Tnf Α ◽

Ifn Γ

CD147, a member of the immunoglobulin (Ig) superfamily, is widely expressed in several cell types. CD147 molecules have multiple cellular functions, such as migration, adhesion, invasion, energy metabolism and T cell activation. In particular, recent studies have demonstrated the potential application of CD147 as an effective therapeutic target for cancer, as well as autoimmune and inflammatory diseases. In this study, we elucidated the functional epitopes on CD147 extracellular domains in T cell regulation using specific monoclonal antibodies (mAbs). Upon T cell activation, the anti-CD147 domain 1 mAbs M6-1E9 and M6-1D4 and the anti-CD147 domain 2 mAb MEM-M6/6 significantly reduced surface expression of CD69 and CD25 and T cell proliferation. To investigate whether functional epitopes of CD147 are differentially expressed on distinct leukocyte subsets, PBMCs, monocyte-depleted PBMCs and purified T cells were activated in the presence of anti-CD147 mAbs. The mAb M6-1E9 inhibited T cell functions via activation of CD147 on monocytes with obligatory cell-cell contact. Engagement of the CD147 epitope by the M6-1E9 mAb downregulated CD80 and CD86 expression on monocytes and IL-2, TNF-α, IFN-γ and IL-17 production in T cells. In contrast, the mAb M6-1D4 inhibited T cell function via activation of CD147 on T cells by downregulating IL-2, TNF-α and IFN-γ. Herein, we demonstrated that certain epitopes of CD147, expressed on both monocytes and T cells, are involved in the regulation of T cell activation.

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