scholarly journals IL-6 Production by Dendritic Cells Is Dispensable for CD8+Memory T-Cell Generation

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jean-François Daudelin ◽  
Mélissa Mathieu ◽  
Salix Boulet ◽  
Nathalie Labrecque
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
Memory T Cells ◽  
T Cell Memory ◽  
Memory Cells ◽  
Differential Outcome ◽  
Memory T Cell ◽  
Antigen Presenting

Following activation, naïve CD8+T cells will differentiate into effectors that differ in their ability to survive: some will persist as memory cells while the majority will die by apoptosis. Signals given by antigen-presenting cells (APCs) at the time of priming modulate this differential outcome. We have recently shown that, in opposition to dendritic cell (DC), CD40-activated B-(CD40-B) cell vaccination fails to efficiently produce CD8+memory T cells. Understanding why CD40-B-cell vaccination does not lead to the generation of functional long-lived memory cells is essential to define the signals that should be provided to naïve T cells by APCs. Here we show that CD40-B cells produce very low amount of IL-6 when compared to DCs. However, supplementation with IL-6 during CD40-B-cell vaccination did not improve memory generation. Furthermore, IL-6-deficient DCs maintained the capacity to promote the formation of functional CD8+effectors and memory cells. Our results suggest that in APC vaccination models, IL-6 provided by the APCs is dispensable for proper CD8+T-cell memory generation.

scholarly journals T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation

2003 ◽  
Vol 197 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Simon Fillatreau ◽  
David Gray
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cell Accumulation ◽  
Antigen Presenting ◽  
Deficient Mice

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

scholarly journals Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors

2008 ◽  
Vol 205 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Max Löhning ◽  
Ahmed N. Hegazy ◽  
Daniel D. Pinschewer ◽  
Dorothea Busse ◽  
Karl S. Lang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Memory T Cells ◽  
Effector T Cells ◽  
Memory Cells ◽  
T Helper ◽  
Cell Therapies ◽  
Memory T Cell

Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon γ–secreting T helper (Th) type 1 and interleukin (IL)-4– or IL-10–secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated vigorously, rapidly modulated IL-7 receptor expression, exhibited partial stability and flexibility of their cytokine patterns, and exerted differential effects on virus-induced immunopathology. Thus, cytokine-secreting effectors can evade activation-induced cell death and develop into long-lived functional memory cells. These findings demonstrate the efficiency of linear memory T cell differentiation and encourage the design of vaccines and immune cell therapies based on differentiated effector T cells.

scholarly journals The CD8+ memory T-cell state of readiness is actively maintained and reversible

Blood ◽  
2009 ◽  
Vol 114 (10) ◽  
pp. 2121-2130 ◽  
Author(s):  
Atef Allam ◽  
Dietrich B. Conze ◽  
Maria Letizia Giardino Torchia ◽  
Ivana Munitic ◽  
Hideo Yagita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Memory T Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Dependent Manner ◽  
Memory Cells ◽  
Memory State ◽  
Memory T Cell

AbstractThe ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cycle state and responded to stimulation like naive T cells, as assessed by proliferation, dependence upon costimulation, and interferon-γ production, without losing cell surface markers associated with memory. The memory state was maintained by signaling via members of the tumor necrosis factor receptor superfamily, CD27 and 4-1BB. Foxo1, a transcription factor involved in T-cell quiescence, was reduced in memory cells, and stimulation of naive CD8 cells via CD27 caused Foxo1 to be phosphorylated and emigrate from the nucleus in a phosphatidylinositol-3 kinase–dependent manner. Consistent with these results, maintenance of G1 in vivo was compromised in antigen-specific memory T cells in vesicular stomatitis virus-infected CD27-deficient mice. Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance.

scholarly journals Human CD14hi monocytes and myeloid dendritic cells provide a cell contact–dependent costimulatory signal for early CD40 ligand expression

Blood ◽  
2011 ◽  
Vol 117 (5) ◽  
pp. 1585-1594 ◽  
Author(s):  
Sagarika Chakrabarty ◽  
James T. Snyder ◽  
Jijia Shen ◽  
Hooman Azmi ◽  
Paul Q. Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Myeloid Dendritic Cells ◽  
A Cell ◽  
Cd40l Expression ◽  
Antigen Presenting

Abstract CD40L on CD4+ T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4+ T cells is highly dependent on a cell-cell interaction with CD14hiCD16− monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14loCD16+ monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus–immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

scholarly journals Deficient Resident Memory T Cell and CD8 T Cell Response to Commensals in Inflammatory Bowel Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 525-537 ◽  
Author(s):  
Alistair Noble ◽  
Lydia Durant ◽  
Lesley Hoyles ◽  
Anne L Mccartney ◽  
Ripple Man ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Antibody Responses ◽  
Memory T Cell ◽  
Cell Responses ◽  
Inflammatory Bowel ◽  
Cellular And Humoral Immunity

Abstract Background and Aims The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD]. Methods Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed. Results Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. Conclusions A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.

scholarly journals Effect of Cyclophosphamide Treatment on Central and Effector Memory T Cells in Mice

2018 ◽  
Vol 37 (5) ◽  
pp. 373-382 ◽  
Author(s):  
Marcin Włodarczyk ◽  
Elżbieta Ograczyk ◽  
Magdalena Kowalewicz-Kulbat ◽  
Magdalena Druszczyńska ◽  
Wiesława Rudnicka ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Immunosuppressive Agent ◽  
Central Memory ◽  
Effector Memory ◽  
Memory Cells ◽  
Memory T Cell ◽  
Effector Memory T Cells ◽  
The Impact

Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. The important question is whether cyclophosphamide (CP), as immunosuppressive agent used in cancer therapy and in some autoimmune diseases, may act on the memory T-cell population. We investigated the effect of CP on the percentage of central memory T cells (TCM) and effector memory T cells (TEM) in the mouse model of CP-induced immunosuppression (8-10-week-old male C57BL/6 mice CP treated for 7 days at the daily dose of 50 μg/g body weight [bw], manifested the best immunosuppression status, as compared to lower doses of CP: 10 or 20 μg/g bw). The CP induced a significant decrease in the percentage of CD8+ (TCM), compared to nonimmunosuppressed mice. This effect was not observed in the case of CD4+ TCM population. The percentage of gated TEM with CD4 and CD8 phenotype was significantly decreased in CP-treated mice, as compared to the control ones. Taken together, the above data indicate that CP-induced immunosuppression in mice leads to a reduction in the abundance of central memory cells possessing preferentially CD8+ phenotype as well as to a reduction in the percentage of effector memory cells (splenocytes both CD4+ and CD8+), compared to the cells from nonimmunosuppressed mice. These findings in mice described in this article may contribute to the understanding of the complexity of the immunological responses in humans and extend research on the impact of the CP model of immunosuppression in mice and memory T-cell populations.

scholarly journals T cell memory is short-lived in the absence of antigen.

1991 ◽  
Vol 174 (5) ◽  
pp. 969-974 ◽  
Author(s):  
D Gray ◽  
P Matzinger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Immunological Memory ◽  
Traditional View ◽  
T Cell Memory ◽  
Memory Cells ◽  
Cell Memory ◽  
Independent State ◽  
Dependent Process

Immunological memory has generally been ascribed to the development of long-lived memory cells that can persist for years in the absence of renewed antigenic encounter. In the experiments reported here, we have adoptively transferred memory T cells in the presence and absence of priming antigen and assessed their functional survival. The results indicate that, in contrast to the traditional view, the maintenance of T cell memory requires the presence of antigen, suggesting that memory, like tolerance, is an antigen-dependent process rather than an antigen-independent state.

scholarly journals CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer

2019 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Memory T Cell ◽  
Draining Lymph Nodes

Abstract Background Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8 + memory T cell subsets including stem memory T cells (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC).Methods Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8 + lymphocyte population. Data were acquired with four-color flow cytometry and analyzed with CellQuest Pro software.Results We observed that 47.65±2.66 of CD8+ lymphocytes expressed the CD45RO marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P=0.024 and P=0.017, respectively). Mean CD96 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO hi TCM and CD45RO low subsets, and TSCM was higher in patients with stage II compared to those with stage I disease (P<0.05). The percentage of naive CD8 + T cells was significantly higher in tumor-involved lymph nodes compared to tumor-free ones (P=0.025).Conclusions Our data collectively indicate no significant differences in the frequencies of CD8 + lymphocytes or their memory T cell subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 low TCM along with naive CD8 + lymphocytes was higher in tumor-involved nodes, which suggests that after long-term exposure to the antigen, and despite the immune reaction in order to provide a pool of effective memory cells, memory cell differentiation is blocked in early-stage (CD45RO low ) due to tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.

scholarly journals Antigen Delivered by Anthrax Lethal Toxin Induces the Development of Memory CD8+ T Cells That Can Be Rapidly Boosted and Display Effector Functions

2007 ◽  
Vol 76 (3) ◽  
pp. 1214-1222 ◽  
Author(s):  
Christine A. Shaw ◽  
Michael N. Starnbach
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Lethal Toxin ◽  
Host Cells ◽  
Effector Memory ◽  
Memory Cells ◽  
Anthrax Lethal Toxin ◽  
Memory T Cell ◽  
Presentation Pathway

ABSTRACT Memory CD8+ T cells are essential for protective immunity against many intracellular pathogens; therefore, stimulation of this population of cells is an important goal of vaccination. We have previously shown that a detoxified derivative of Bacillus anthracis anthrax lethal toxin (LT) can deliver heterologous CD8+ T-cell epitopes to the major histocompatibility complex class I processing and presentation pathway of murine host cells and that immunization of mice with these LT-antigen fusion proteins leads to the induction of antigen-specific CD8+ T cells. In this report we extend these findings to include a detailed characterization of the phenotypic and functional properties of the T cells stimulated by the LT-based system. We found that after an initial period of expansion and contraction, antigen-specific CD8+ T cells differentiated into a pool of memory cells that produced gamma interferon and displayed in vivo cytotoxic activity. The transition to memory cells appeared to be quite rapid based on an analysis of the phenotypic marker CD127 and the effectiveness of a booster immunization administered early after the initial immunization. We also investigated the composition of the memory T-cell pool induced by this system and found that while one immunization induced a mixture of effector memory T cells (CD62Llow) and central memory T cells (CD62Lhigh), a second immunization preferentially elevated the effector memory T-cell frequency. Finally, we demonstrated that mice that received prime-boost immunizations of LT-antigen proteins were more protected in a Listeria monocytogenes challenge model than mice that received only one immunization.

scholarly journals A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation.

1994 ◽  
Vol 180 (5) ◽  
pp. 1829-1840 ◽  
Author(s):  
D J Cassell ◽  
R H Schwartz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Quantitative Analysis ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Costimulatory Signals ◽  
Antigen Presenting ◽  
Activated B Cells

Ligation of CD28 on CD4 Th1 clones and freshly isolated mixtures of naive and memory CD4 T cells triggered their T cell receptors (TCR) is sufficient to induce the costimulatory signals necessary for interleukin 2 (IL-2) production by these cells. CTLA-4-reactive ligands expressed on antigen-presenting cells (APC) are critical in providing costimulatory signals to these T cell populations. We demonstrate that these activation characteristics apply equally to purified naive CD4 T cells. Because B cell blasts express CTLA-4-reactive ligands and high levels of adhesion and major histocompatibility complex class II molecules, they would be expected to engage both the TCR and CD28 and consequently stimulate IL-2 production by naive CD4 T cells. Using purified populations of cells in limiting dilution cultures, we have carried out a quantitative analysis of the interaction between naive CD4 T cells and either activated B or dendritic cells. We demonstrate that B cell blasts stimulate a high frequency of naive CD4 T cells. Slight differences in TCR signaling efficiency between the two APC types were observed. Even at optimal peptide concentrations, however, the amount of IL-2 made by individual T cells was fourfold lower in response to B cell blasts than to dendritic cells. This relative deficiency of activated B cells was due to their inability to optimally costimulate naive CD4 T cells.

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