scholarly journals Chemokine Receptor 5 Is Dispensable for Innate and Adaptive Immune Responses to Listeria monocytogenes Infection

2004 ◽  
Vol 72 (2) ◽  
pp. 1057-1064 ◽  
Author(s):  
Maggie X. Zhong ◽  
William A. Kuziel ◽  
Eric G. Pamer ◽  
Natalya V. Serbina
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
Immune Responses ◽  
Chemokine Receptor ◽  
Cd8 T Cells ◽  
Interleukin 12 ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Hiv 1 ◽  
Chemokine Receptor 5

ABSTRACT Chemokine receptor 5 (CCR5) binds macrophage inflammatory protein 1α (MIP-1α), MIP-1β, RANTES, and members of the monocyte chemotactic protein family and is also a receptor for human immunodeficiency virus (HIV). CCR5 ligands can suppress HIV-1 entry into cells. In humans, homozygous mutations of the ccr5 gene confer resistance to HIV-1 infection. The role of CCR5 in defense against microbial infection is unclear. In this study we examined the innate and adaptive immune responses of CCR5-deficient mice to the intracellular bacterial pathogen Listeria monocytogenes. We found that migration of monocytic cells, formation of L. monocytogenes-containing lesions, and bacterial clearance occurred normally in the spleens and livers of CCR5-deficient animals. Activation of macrophages and dendritic cells during the first 3 days postinfection was normal in the absence of CCR5, as demonstrated by intact expression of inducible nitric oxide synthase (iNOS) and production of the cytokines tumor necrosis factor alpha, gamma interferon, and interleukin-12. Priming of L. monocytogenes-specific CD8 T cells also occured independently of CCR5 expression. Previously immunized, CCR5-deficient animals mounted normal secondary CD8 T-cell responses and cleared bacteria from infected organs similarly to wild-type controls, suggesting that CCR5 is dispensable for migration and activation of memory CD8 T cells. Our data indicate that CCR5-mediated chemotaxis is not required for defense against infection with L. monocytogenes.

scholarly journals 62: Sensing and Alarm Function of Mucosal Memory CD8 T Cells Trigger Innate and Adaptive Immune Responses

2015 ◽  
Vol 143 (suppl_1) ◽  
pp. A034-A034 ◽  
Author(s):  
Jason M. Schenkel ◽  
Kathryn A. Fraser ◽  
Lalit K. Beura ◽  
Kristen E. Pauken ◽  
David Masopust ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Adaptive Immune Responses ◽  
Memory Cd8 T Cells ◽  
Adaptive Immune

scholarly journals Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5868-5877 ◽  
Author(s):  
Matthew P. Morrow ◽  
Panyupa Pankhong ◽  
Dominick J. Laddy ◽  
Kimberly A. Schoenly ◽  
Jian Yan ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Dna Vaccination ◽  
Vaccine Adjuvant ◽  
Cell Populations ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Strong Candidate ◽  
First Time

Abstract Improving the potency of immune responses is paramount among issues concerning vaccines against deadly pathogens. IL-28B belongs to the newly described interferon lambda (IFNλ) family of cytokines, and has not yet been assessed for its potential ability to influence adaptive immune responses or act as a vaccine adjuvant. We compared the ability of plasmid-encoded IL-28B to boost immune responses to a multiclade consensus HIV Gag plasmid during DNA vaccination with that of IL-12. We show here that IL-28B, like IL-12, is capable of robustly enhancing adaptive immunity. Moreover, we describe for the first time how IL-28B reduces regulatory T-cell populations during DNA vaccination, whereas IL-12 increases this cellular subset. We also show that IL-28B, unlike IL-12, is able to increase the percentage of splenic CD8+ T cells in vaccinated animals, and that these cells are more granular and have higher antigen-specific cytolytic degranulation compared with cells taken from animals that received IL-12 as an adjuvant. Lastly, we report that IL-28B can induce 100% protection from mortality after a lethal influenza challenge. These data suggest that IL-28B is a strong candidate for further studies of vaccine or immunotherapy protocols.

scholarly journals Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

2020 ◽  
Author(s):  
Kuai Yu ◽  
Yongjian Wu ◽  
Jingjing He ◽  
Xuefei Liu ◽  
Bo Wei ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Severe Disease ◽  
Adaptive Immune Responses ◽  
Activated T Cells ◽  
Adaptive Immune ◽  
The Impact ◽  
Excessive Activation

Abstract Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed dysregulated adaptive immune responses in patients with severe disease. A new cluster of excessively activated CD8 T cells (Tea) was further identified, which displayed exhausted phenotypes and diminished function of antigen recognition. Interestingly, expression of PTMA, the proprotein of Tα1, was significantly increased in a group of highly proliferating CD8 T cells with memory stem cell features. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

IL-8 responsiveness defines a subset of CD8 T cells poised to kill

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3463-3471 ◽  
Author(s):  
Christoph Hess ◽  
Terry K. Means ◽  
Patrick Autissier ◽  
Tonia Woodberry ◽  
Marcus Altfeld ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chemokine Receptor ◽  
Cd8 T Cells ◽  
Molecular Mechanisms ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Immune System Activation ◽  
Hiv 1

CD8 T cells play a key role in host defense against intracellular pathogens. Efficient migration of these cells into sites of infection is therefore intimately linked to their effector function. The molecular mechanisms that control CD8 T-cell trafficking into sites of infection and inflammation are not well understood, but the chemokine/chemokine receptor system is thought to orchestrate this process. Here we systematically examined the chemokine receptor profile expressed on human CD8 T cells. Surprisingly, we found that CXC chemokine receptor 1 (CXCR1), the predominant neutrophil chemokine receptor, defined a novel interleukin-8/CXC ligand 8 (IL-8/CXCL8)–responsive CD8 T-cell subset that was enriched in perforin, granzyme B, and interferon-γ (IFNγ), and had high cytotoxic potential. CXCR1 expression was down-regulated by antigen stimulation both in vitro and in vivo, suggesting antigen-dependent shaping of the migratory characteristics of CD8 T cells. On virus-specific CD8 T cells from persons with a history of Epstein-Barr virus (EBV) and influenza infection, CXCR1 expression was restricted to terminally differentiated effector memory cells. In HIV-1 infection, CXCR1-expressing HIV-1–specific CD8 T cells were present only in persons who were able to control HIV-1 replication during structured treatment interruptions. Thus, CXCR1 identifies a subset of CD8 T cells poised for immediate cytotoxicity and early recruitment into sites of innate immune system activation.

Enumeration of human antigen–specific naive CD8+ T cells reveals conserved precursor frequencies

Blood ◽  
2010 ◽  
Vol 115 (18) ◽  
pp. 3718-3725 ◽  
Author(s):  
Cécile Alanio ◽  
Fabrice Lemaitre ◽  
Helen K. W. Law ◽  
Milena Hasan ◽  
Matthew L. Albert
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Vaccine Development ◽  
Direct Detection ◽  
Magnetic Bead ◽  
Cell Precursor ◽  
Adaptive Immune ◽  
Precursor Frequency ◽  
Magnetic Bead Enrichment ◽  
Hiv 1

Abstract The number of antigen-specific naive CD8+ T cells is believed to be important in the shaping of adaptive immune responses, and is predictive for the magnitude of priming responses in mouse models. Because of extremely low precursor frequencies, knowledge about these cells comes from indirect techniques and estimations. Here, we present a strategy based on the combination of tetramer staining, magnetic-bead enrichment, and multiparametric cytometry, which permitted direct detection and analysis of CD8+ T cells reactive for 6 different naive epitopes (MART-126-35, HIV-1 Gag p1777-85, hepatitis C virus [HCV] NS31406-1415, HCV Core132-140, NY-ESO-1157-165, and cytomegalovirus [CMV] pp65495-503). Interestingly, we detected higher than 100-fold differences in precursor frequency across these epitopes (from 0.6 × 10−6 to 1.3 × 10−4), but conserved frequencies among humans. Development of a procedure for direct assessment of T-cell precursor frequency in humans has important implications, with particular relevance to vaccine development and monitoring of tumor and self-reactive T cells.

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