Murine plasmacytoid dendritic cells induce effector/memory CD8+ T-cell responses in vivo after viral stimulation

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1808-1815 ◽  
Author(s):  
Géraldine Schlecht ◽  
Sylvie Garcia ◽  
Nicolas Escriou ◽  
Antonio A. Freitas ◽  
Claude Leclerc ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Plasmacytoid Dendritic Cells ◽  
Effector Memory ◽  
Cell Responses ◽  
Memory Cd8 T Cell

Abstract Like their human counterparts, mouse plasmacytoid dendritic cells (pDCs) play a central role in innate immunity against viral infections, but their capacity to prime T cells in vivo remains unknown. We show here that virus-activated pDCs differentiate into antigen-presenting cells able to induce effector/memory CD8+ T-cell responses in vivo against both epitopic peptides and endogenous antigen, whereas pDCs activated by synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG) acquire only the ability to recall antigen-experienced T-cell responses. We also show that immature pDCs are unable to induce effector or regulatory CD8+ T-cell responses. Thus, murine pDCs take part in both innate and adaptive immune responses by directly priming naive CD8+ T cells during viral infection.

scholarly journals Role of Tumor Suppressor TSC1 in Regulating Antigen-Specific Primary and Memory CD8 T Cell Responses to Bacterial Infection

2014 ◽  
Vol 82 (7) ◽  
pp. 3045-3057 ◽  
Author(s):  
Sruti Krishna ◽  
Jialong Yang ◽  
Hongxia Wang ◽  
Yurong Qiu ◽  
Xiao-Ping Zhong
Keyword(s):  
T Cell ◽  
Bacterial Infection ◽  
Adoptive Transfer ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Cell Responses ◽  
Memory Cd8 T Cell

ABSTRACTThe serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) integrates various environmental cues such as the presence of antigen, inflammation, and nutrients to regulate T cell growth, metabolism, and function. The tuberous sclerosis 1 (TSC1)/TSC2 complex negatively regulates the activity of an mTOR-containing multiprotein complex called mTOR complex 1. Recent studies have revealed an essential cell-intrinsic role for TSC1 in T cell survival, quiescence, and mitochondrial homeostasis. Given the emerging role of mTOR activity in the regulation of the quantity and quality of CD8 T cell responses, in this study, we examine the role of its suppressor, TSC1, in the regulation of antigen-specific primary and memory CD8 T cell responses to bacterial infection. Using an established model system of transgenic CD8 cell adoptive transfer and challenge withListeria monocytogenesexpressing a cognate antigen, we found that TSC1 deficiency impairs antigen-specific CD8 T cell responses, resulting in weak expansion, exaggerated contraction, and poor memory generation. Poor expansion of TSC1-deficient cells was associated with defects in survival and proliferationin vivo, while enhanced contraction was correlated with an increased ratio of short-lived effectors to memory precursors in the effector cell population. This perturbation of effector-memory differentiation was concomitant with decreased expression of eomesodermin among activated TSC1 knockout cells. Upon competitive adoptive transfer with wild-type counterparts and antigen rechallenge, TSC1-deficient memory cells showed moderate defects in expansion but not cytokine production. Taken together, these findings provide direct evidence of a CD8 T cell-intrinsic role for TSC1 in the regulation of antigen-specific primary and memory responses.

scholarly journals Imatinib Mesylate Inhibits Antigen-Specific Memory CD8 T Cell Responses In Vivo

2007 ◽  
Vol 178 (4) ◽  
pp. 2028-2037 ◽  
Author(s):  
Parisa Sinai ◽  
Rance E. Berg ◽  
J. Marshall Haynie ◽  
Merrill J. Egorin ◽  
Robert L. Ilaria ◽  
...  
Keyword(s):  
T Cell ◽  
Imatinib Mesylate ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Specific Memory ◽  
Memory Cd8 T Cell

scholarly journals Adrenergic signaling controls early transcriptional programs during CD8+ T cell responses to viral infection

2021 ◽  
Author(s):  
Leonardo Estrada ◽  
Didem Agac Cobanoglu ◽  
Aaron Wise ◽  
Robert Maples ◽  
Murat Can Cobanoglu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Receptor Activation ◽  
Cell Development ◽  
Primary Response ◽  
Cell Responses

Viral infections drive the expansion and differentiation of responding CD8+ T cells into variegated populations of cytolytic effector and memory cells. While pro-inflammatory cytokines and cell surface immune receptors play a key role in guiding T cell responses to infection, T cells are also markedly influenced by neurotransmitters. Norepinephrine is a key sympathetic neurotransmitter, which acts to suppress CD8 + T cell cytokine secretion and lytic activity by signaling through the beta2-adrenergic receptor (ADRB2). Although ADRB2 signaling is considered generally immunosuppressive, its role in regulating differentiation of effector T cells in response to infection has not been investigated. Using an adoptive transfer approach, we compared the expansion and differentiation of wild type (WT) to Adrb2-/- CD8 + T cells throughout the primary response to vesicular stomatitis virus (VSV) infection in vivo. We measured the dynamic changes in transcriptome profiles of antigen-specific CD8 + T cells as they responded to VSV. Within the first 7 days of infection, WT cells out-paced the expansion of Adrb2-/- cells, which correlated with reduced expression of IL-2 and the IL-2Ralpha; in the absence of ADRB2. RNASeq analysis identified over 300 differentially expressed genes that were both temporally regulated following infection and selectively regulated in WT vs Adrb2-/- cells. These genes contributed to major transcriptional pathways including cytokine receptor activation, signaling in cancer, immune deficiency, and neurotransmitter pathways. By parsing genes within groups that were either induced or repressed over time in response to infection, we identified three main branches of genes that were differentially regulated by the ADRB2. These gene sets were predicted to be regulated by specific transcription factors involved in effector T cell development, such as Tbx21 and Eomes. Collectively, these data demonstrate a significant role for ADRB2 signaling in regulating key transcriptional pathways during CD8 + T cells responses to infection that may dramatically impact their functional capabilities and downstream memory cell development.

scholarly journals TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 967-977 ◽  
Author(s):  
Agostinho Carvalho ◽  
Antonella De Luca ◽  
Silvia Bozza ◽  
Cristina Cunha ◽  
Carmen D'Angelo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Aspergillus Fumigatus ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Class I ◽  
Class I Mhc ◽  
Cell Responses ◽  
Memory Cd8 T Cell

Abstract Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8+ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8+ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients.

scholarly journals IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists

2016 ◽  
Vol 197 (1) ◽  
pp. 168-178 ◽  
Author(s):  
Mélanie Desbois ◽  
Pauline Le Vu ◽  
Clélia Coutzac ◽  
Elie Marcheteau ◽  
Coralie Béal ◽  
...  
Keyword(s):  
T Cell ◽  
Antitumor Activity ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Cell Responses ◽  
Memory Cd8 T Cell

scholarly journals Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Aránzazu Cruz-Adalia ◽  
Guillermo Ramirez-Santiago ◽  
Jesús Osuna-Pérez ◽  
Mónica Torres-Torresano ◽  
Virgina Zorita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Bacterial Antigens ◽  
Memory Cd8 T Cell

scholarly journals Regulatory CD4+CD25+ T Cells Restrict Memory CD8+ T Cell Responses

2002 ◽  
Vol 196 (12) ◽  
pp. 1585-1592 ◽  
Author(s):  
Mischo Kursar ◽  
Kerstin Bonhagen ◽  
Joachim Fensterle ◽  
Anne Köhler ◽  
Robert Hurwitz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Secondary Infection ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cell Responses ◽  
Boost Immunization ◽  
Memory Cd8 T Cell

CD4+ T cell help is important for the generation of CD8+ T cell responses. We used depleting anti-CD4 mAb to analyze the role of CD4+ T cells for memory CD8+ T cell responses after secondary infection of mice with the intracellular bacterium Listeria monocytogenes, or after boost immunization by specific peptide or DNA vaccination. Surprisingly, anti-CD4 mAb treatment during secondary CD8+ T cell responses markedly enlarged the population size of antigen-specific CD8+ T cells. After boost immunization with peptide or DNA, this effect was particularly profound, and antigen-specific CD8+ T cell populations were enlarged at least 10-fold. In terms of cytokine production and cytotoxicity, the enlarged CD8+ T cell population consisted of functional effector T cells. In depletion and transfer experiments, the suppressive function could be ascribed to CD4+CD25+ T cells. Our results demonstrate that CD4+ T cells control the CD8+ T cell response in two directions. Initially, they promote the generation of a CD8+ T cell responses and later they restrain the strength of the CD8+ T cell memory response. Down-modulation of CD8+ T cell responses during infection could prevent harmful consequences after eradication of the pathogen.

Sign in / Sign up

Export Citation Format

Share Document