scholarly journals 54P AKT inhibition during ex vivo tumor-infiltrating lymphocyte (TIL) expansion enhances cytokine production and function while increasing the population of less differentiated (CD39-CD69-) CD8+ T-cells

2021 ◽  
Vol 32 ◽  
pp. S1395
Author(s):  
R. Cubas ◽  
A. Yuhas ◽  
M. Machin ◽  
Y. Zhang
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Tumor Infiltrating Lymphocyte ◽  
And Function

scholarly journals Regulation of Cytokine Production by Virus-Specific CD8 T Cells in the Lungs

2008 ◽  
Vol 82 (16) ◽  
pp. 7799-7811 ◽  
Author(s):  
Ross B. Fulton ◽  
Matthew R. Olson ◽  
Steven M. Varga
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Memory T Cells ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Lung Parenchyma ◽  
Host Cells ◽  
Peripheral Tissues ◽  
Specific Memory

ABSTRACT Inflammation and the elimination of infected host cells during an immune response often cause local tissue injury and immunopathology, which can disrupt the normal functions of tissues such as the lung. Here, we show that both virus-induced inflammation and the host tissue environment combine to influence the capacity of virus-specific CD4 and CD8 T cells to produce cytokines in various tissues. Decreased production of cytokines, such as IFN-γ and TNF-α, by antigen-specific T cells is more pronounced in peripheral tissues, such as the lung and kidney, than in secondary lymphoid organs, such as the spleen or lymph nodes. We also demonstrate that tissues regulate cytokine production by memory T cells independently of virus infection, as memory T cells that traffic into the lungs of naïve animals exhibit a reduced ability to produce cytokines following direct ex vivo peptide stimulation. Furthermore, we show that cytokine production by antigen-specific memory CD4 and CD8 T cells isolated from the lung parenchyma can be rescued by stimulation with exogenous peptide-pulsed antigen-presenting cells. Our results suggest that the regulation of T-cell cytokine production by peripheral tissues may serve as an important mechanism to prevent immunopathology and preserve normal tissue function.

IL-15 enhances survival and function of HIV-specific CD8+ T cells

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 1024-1029 ◽  
Author(s):  
Yvonne M. Mueller ◽  
Paul M. Bojczuk ◽  
E. Scott Halstead ◽  
Alfred H. J. Kim ◽  
James Witek ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Interferon Γ ◽  
Effector Function ◽  
Effector Memory ◽  
Antiviral Function ◽  
Induced Apoptosis ◽  
And Function

AbstractHIV-specific CD8+ T cells are prone to undergo apoptosis, and this may affect their ability to control HIV infection. Because CD8-mediated immune responses play a key role in controlling HIV infection, enhancing the survival and effector function of HIV-specific CD8+ T cells may augment their ability to control HIV virus. We show here that interleukin 15 (IL-15) potently inhibits spontaneous and CD95/Fas-induced apoptosis of HIV-specific CD8+ T cells. IL-15 inhibits apoptosis in both CD45RA−CD62L− and CD45RA+CD62L− effector memory subpopulations of these cells. Furthermore, IL-15 greatly enhances the survival of HIV-specific CD8+ T cells in long-term cultures. Finally, IL-15 directly enhances activation, interferon γ (IFNγ) production, and direct ex vivo cytotoxicity of HIV-specific CD8+ T cells. Thus, IL-15 potently enhances the survival and effector function of HIV-specific CD8+ T cells and, therefore, may prove useful in augmenting the antiviral function of these cells.

scholarly journals Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 422-433 ◽  
Author(s):  
Lucy J. Walker ◽  
Yu-Hoi Kang ◽  
Matthew O. Smith ◽  
Hannah Tharmalingham ◽  
Narayan Ramamurthy ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Receptor Expression ◽  
Mait Cells ◽  
Distinct Phenotype ◽  
Cell Pool ◽  
Tc17 Cells ◽  
And Function ◽  
Functional Analyses

Human mucosal associated invariant T (MAIT) CD8+ and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 (++) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161++CD8αβ+ T cells exist in cord blood, from which a prominent MAIT cell (TCR Vα7.2+) population emerges post-natally. During this expansion, CD8αα T cells appear exclusively within a CD161++CD8+/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161++CD8αβ+ counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161++CD8+ T-cell pool and the distinct phenotype and function of CD8αα cells in man.

Decreased Expression and Function of Vß6+ and Vß14+ T Cells is Associated with Decreased Th1 Cytokine Production in Mice with Plasma Cell Tumors

1996 ◽  
Vol 82 (1) ◽  
pp. 22-26 ◽  
Author(s):  
Heather E. Stefanski ◽  
Ambika Mathur
Keyword(s):  
T Cells ◽  
Plasma Cell ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Cell Tumor ◽  
Cell Surface Expression ◽  
Ifn Gamma ◽  
Plasma Cell Tumor ◽  
Th1 Cytokine ◽  
And Function

Aims and background We have found that polyclonally stimulated T cells from mice bearing ascitic plasma cell tumors demonstrate specific decreases in Th1 cytokine production. In this study we investigated whether loss of Th1 responses in the plasma cell tumor system was associated with alterations in the Vß T cell receptor repertoire. Methods We examined the cell surface expression of specific Vß expressing splenic CD4+ or CD8+ T cells from normal and tumor bearing mice using direct three-color flowcytometry. In order to determine the Th phenotype of Vß expressing T cells, we enriched for Vß6, Vß14 or Vß8.1,8.2 cells, polyclonally stimulated them and measured the levels of the cytokines interleukin-4 (IL-4), IL-2 and interferon-gamma (IFN-gamma). Results We find that there is a statistically significant decrease in the frequency of Vß6+ and Vß14+ CD8+ T cells in mice bearing a plasma cell tumor (B53) as compared to normals (p<0.05). Stimulated Vß6+ and Vß14+ T cells exhibit an exclusively Th1 phenotype. Stimulated Vß6+ and Vß14+ T cells from B53 mice are deficient in production of the Th1 cytokines. In contrast, stimulated Vß8.1,8.2+ T cells, which are not altered in B53 mice, reveal a Th2 phenotype. Conclusions The significance of this study is our demonstration that decreased expression and function of Vß6+ and Vß14+ T cells may be, at least in part, responsible for the decrease in the production of IL-2 and/or IFN-gamma observed in hosts with tumors.

scholarly journals Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses

2020 ◽  
Vol 4 (10) ◽  
pp. 2143-2157 ◽  
Author(s):  
Alak Manna ◽  
Timothy Kellett ◽  
Sonikpreet Aulakh ◽  
Laura J. Lewis-Tuffin ◽  
Navnita Dutta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Dependent Manner

Abstract Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.

scholarly journals Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells

2019 ◽  
Vol 8 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Alexandra E. Turley ◽  
Joseph W. Zagorski ◽  
Rebekah C. Kennedy ◽  
Robert A. Freeborn ◽  
Jenna K. Bursley ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Low Dose ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Cadmium Exposure ◽  
Activated T Cells ◽  
Low Level

The purpose of this study was to determine the effect of subchronic, oral, low-dose cadmium exposure (32 ppm over 10 weeks) on the rat immune system. We found that cadmium exposure increased the induction of IFNγ and IL-10 in T cells activated ex vivo after cadmium exposure.

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