scholarly journals The Wild-Type Sequence (wt) p5325–35 Peptide Induces HLA-DR7 and HLA-DR11-Restricted CD4+ Th Cells Capable of Enhancing the Ex Vivo Expansion and Function of Anti-wt p53264–272 Peptide CD8+ T Cells

2006 ◽  
Vol 177 (10) ◽  
pp. 6795-6803 ◽  
Author(s):  
Daisuke Ito ◽  
Andreas Albers ◽  
Yong Xiang Zhao ◽  
Carmen Visus ◽  
Ettore Appella ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Wild Type ◽  
Th Cells ◽  
Wild Type Sequence ◽  
And Function ◽  
Type Sequence

Large Ex Vivo Expansion of Human Umbilical Cord Blood CD4+ and CD8+ T Cells

1999 ◽  
Vol 8 (2) ◽  
pp. 129-139 ◽  
Author(s):  
Danna Skea ◽  
Nan-Hua Chang ◽  
Robin Hedge ◽  
Barbara Dabek ◽  
Truman Wong ◽  
...  
Keyword(s):  
T Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Cd8 T Cells ◽  
Umbilical Cord Blood ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

scholarly journals Human Bone Marrow Derived Mesenchymal Stromal Cells Enhance the Number and Function of Umbilical Cord Blood Peripheral Tregs during IL-2 Driven Ex Vivo Expansion

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1116-1116
Author(s):  
Jeong-Su Do ◽  
Alex Y. Huang ◽  
Daniel Zwick ◽  
Fei Zhong ◽  
David Askew ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Foxp3 Expression ◽  
Ex Vivo Expansion ◽  
Mitochondrial Transfer ◽  
And Function

Abstract Tumor growth factor β (TGF-β)-induced peripheral regulatory T cells (pTreg) are a promising therapeutic cell source that exhibit Foxp3 expression and suppressive functions similar to natural regulatory T cells. Nonetheless, their clinical potential is limited by the instability of Foxp3 expression and T cell exhaustion that occurs during ex vivo expansion. We postulated that mesenchymal stromal cells (MSCs) could enhance the number, function and Foxp3 expression stability of pTregs during IL-2 driven 21 day expansion due to their diverse immunomodulatory properties. In this study, we observed that use of a human bone marrow mesenchymal stromal cells (hBM-MSC) platform significantly enhanced the number of pTreg during IL-2 driven 21 day ex vivo expansion vs. standard suspension culture condition (MSC platform: 80.2 x 106 vs. IL2/media: 39.3 x 106, n=6; p<0.01). Also the number of pTreg expressing a naive phenotype (CD4+CD45RA+ and CD4+CD62L+ ) were significantly increased (CD45RA+; MSC platform: 74.4 ± 1.6 x 106 vs. IL2/media: 45.9 ± 2.9 x 106, n=6, p<0.001; CD62L+; MSC platform: 79.1 ± 1.3 x 106 vs. IL2/media: 54.5 ± 2.1 x 106, n=6, p<0.001), as well as stability of Foxp3 expression (IL-2/media: 88.2 ± 1.7% vs. MSC platform: 96.2 ± 1.1%, n=7; p<0.05). In addition, pTreg suppressive function was noted to be more potent during 21 day IL-2 driven ex vivo expansion compared to standard IL-2/media culture condition (MSC platform: 79% vs. media: 35% inhibition of T cell proliferation in 10:1 ratio, n=6; p<0.01). pTreg expanded over a hBM-MSC platform exhibited higher surface CD25, CTLA-4, and ICOS MFI expression (CD25; MSC platform: 1410 vs. Media: 774; p<0.001, CTLA-4; MSC platform: 1084 vs. Media: 318; p<0.001, ICOS; MSC platform: 4386 vs. Media: 2641, p<0.01, n=6). Notably, hBM-MSC enhancement of pTreg ex vivo expansion requires direct cell-cell contact, as Foxp3 expression in pTreg was not enhanced by hBM-MSC conditioned media (CM:73.4 ± 6.8% vs. MSC platform: 96.2 ± 1.0%, p<0.001; and IL2/media: 88.8 ± 1.6% vs. MSC platform: 96.2 ± 1.0%, p<0.01) nor in a trans-well culture experiments (Transwell: 83.4 ± 2.5% vs. IL2/media: 88.8 ± 1.6%; and Transwell: 83.4 ± 2.5% vs. MSC platform: 96.2 ± 1.0%, p<0.01). Importantly, optical sectioning microscopy and flow cytometry revealed that hBM-MSC supports Treg number and function via direct contact-dependent mitochondrial transfer (Figure 1A-B). Cytochalasin B treatment blocked mitochondrial transfer, suggesting that tunneling nanotubes (TNT) facilitate mitochondrial transfer from hBM-MSC to pTreg during IL-2 driven ex vivo expansion (Mock: 2208 ± 122.1 vs. Cyto B: 923.8 ± 89 MFI, n=6, p<0.0001). Moreover, the quantity of ATP (n=6; p<0.01) mitochondrial potential of pTreg (MSC platform: 9010 ± 224.5 vs. media: 7316 ± 122.7 MFI, n=6; p<0.01) were significantly enhanced in pTreg during IL-2 driven ex vivo expansion over a hBM-MSC platform. Taken together, hBM-MSC significantly improves the number, maturation, and function of pTreg during 21 day IL-2 driven ex vivo expansion. We have identified one key mechanism of action of hBM-MSC underlying these favorable effects on pTreg during ex vivo expansion to be mitochondrial transfer via TNT. Notably, these studies identify a novel role of hBM-MSC to overcome current limitations in IL-2/media suspension culture conditions including T cell senescence, and loss of Foxp3 expression. Disclosures No relevant conflicts of interest to declare.

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 Clinically-relevant T cell expansion protocols activate distinct cellular metabolic programs and phenotypes

2021 ◽  
Author(s):  
Sarah MacPherson ◽  
Sarah Keyes ◽  
Marisa K Kilgour ◽  
Julian Smazynski ◽  
Jessica Sudderth ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Cell Function ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Metabolic Phenotypes ◽  
T Cell Function ◽  
T Cell Expansion ◽  
And Function

Ex vivo expansion conditions used to generate T cells for immunotherapy are thought to adopt metabolic phenotypes that impede therapeutic efficacy in vivo. The comparison of five different culture media used for clinical T cell expansion revealed unique optima based on different output variables including proliferation, differentiation, function, activation and mitochondrial phenotypes. T cells adapted their metabolism to match their media expansion condition as shown by glucose and glutamine uptake, and patterns of glucose isotope labeling. However, adoption of these metabolic phenotypes was uncoupled to T cell function. Furthermore, T cell products cultured in ascites from ovarian cancer patients displayed suppressed mitochondrial activity and function irrespective of the ex vivo expansion media. In one case, culturing in ascites resulted in increased glucose uptake which was insufficient to rescue T cell function. Thus, ex vivo T cell expansion conditions have profound impacts on metabolism and function.

scholarly journals Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30229 ◽  
Author(s):  
Marcus O. Butler ◽  
Osamu Imataki ◽  
Yoshihiro Yamashita ◽  
Makito Tanaka ◽  
Sascha Ansén ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Cd4 T Cell ◽  
Cd4 T Cell Help ◽  
T Cell Help

scholarly journals Generation of T Cells Specific for the Wild-Type Sequence p53264–272 Peptide in Cancer Patients: Implications for Immunoselection of Epitope Loss Variants

2000 ◽  
Vol 165 (10) ◽  
pp. 5938-5944 ◽  
Author(s):  
Thomas K. Hoffmann ◽  
Koji Nakano ◽  
Elaine M. Elder ◽  
Grzegorz Dworacki ◽  
Sydney D. Finkelstein ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Patients ◽  
Wild Type ◽  
Wild Type Sequence ◽  
Type Sequence

scholarly journals Characteristics of Malignant Pleural Effusion Resident CD8+ T Cells from a Heterogeneous Collection of Tumors

2020 ◽  
Vol 21 (17) ◽  
pp. 6178
Author(s):  
Rajeev Dhupar ◽  
Olugbenga T. Okusanya ◽  
Seth H. Eisenberg ◽  
Sara E. Monaco ◽  
Ayana T. Ruffin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Pleural Effusion ◽  
Cd8 T Cells ◽  
Malignant Pleural Effusion ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Great Promise ◽  
Primary Tumors ◽  
Indwelling Catheters

While T cell-based cancer immunotherapies have shown great promise, there remains a need to understand how individual metastatic tumor environments impart local T cell dysfunction. At advanced stages, cancers that metastasize to the pleural space can result in a malignant pleural effusion (MPE) that harbors abundant tumor and immune cells, often exceeding 108 leukocytes per liter. Unlike other metastatic sites, MPEs are readily and repeatedly accessible via indwelling catheters, providing an opportunity to study the interface between tumor dynamics and immunity. In the current study, we examined CD8+ T cells within MPEs collected from patients with heterogeneous primary tumors and at various stages in treatment to determine (1) if these cells possess anti-tumor activity following removal from the MPE, (2) factors in the MPE that may contribute to their dysfunction, and (3) the phenotypic changes in T cell populations that occur following ex vivo expansion. Co-cultures of CD8+ T cells with autologous CD45― tumor containing cells demonstrated cytotoxicity (p = 0.030) and IFNγ production (p = 0.003) that inversely correlated with percent of myeloid derived suppressor cells, lactate, and lactate dehydrogenase (LDH) within the MPE. Ex vivo expansion of CD8+ T cells resulted in progressive differentiation marked by distinct populations expressing decreased CD45RA, CCR7, CD127, and increased inhibitory receptors. These findings suggest that MPEs may be a source of tumor-reactive T cells and that the cellular and acellular components suppress optimal function.

Sign in / Sign up

Export Citation Format

Share Document