The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells

Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria.

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Strong SARS-CoV-2 N-specific CD8+ T immunity induced by engineered extracellular vesicles associates with protection from lethal infection in mice.

10.1101/2022.01.10.475620 ◽

2022 ◽

Author(s):

Flavia Ferrantelli ◽

Chiara Chiozzini ◽

Francesco Manfredi ◽

Patrizia Leone ◽

Massimo Spada ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Extracellular Vesicles ◽

Cd8 T Cell ◽

New Combination ◽

Immune Memory ◽

Lethal Challenge ◽

Cd8 T Lymphocytes ◽

Cell Immunity ◽

Anchoring Protein

SARS-CoV-2-specific CD8+ T cell immunity is expected to counteract viral variants in both efficient and durable ways. We recently described a way to induce a potent SARS-CoV-2 CD8+ T immune response through the generation of engineered extracellular vesicles (EVs) emerging from muscle cells. This method relies on intramuscular injection of DNA vectors expressing different SARS-CoV-2 antigens fused at their N-terminus with Nefmut protein, i.e., a very efficient EV-anchoring protein. However, quality, tissue distribution, and efficacy of these SARS-CoV-2-specific CD8+ T cells remained uninvestigated. To fill the gaps, antigen-specific CD8+ T lymphocytes induced by the immunization through the Nefmut-based method were characterized in terms of their polyfunctionality and localization at lung airways, i.e., the primary targets of SARS-CoV-2 infection. We found that injection of vectors expressing Nefmut/S1 and Nefmut/N generated polyfunctional CD8+ T lymphocytes in both spleens and bronchoalveolar lavage fluids (BALFs). When immunized mice were infected with 4.4 lethal doses 50% of SARS-CoV-2, all S1-immunized mice succumbed, whereas those developing the highest percentages of N-specific CD8+ T lymphocytes resisted the lethal challenge. We also provide evidence that the N-specific immunization coupled with the development of antigen-specific CD8+ T-resident memory cells in lungs, supporting the idea that the Nefmut-based immunization can confer a long-lasting, lung-specific immune memory. In view of the limitations of current anti-SARS-CoV-2 vaccines in terms of antibody waning and efficiency against variants, our CD8+ T cell-based platform could be considered for a new combination prophylactic strategy.

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Dendritic Cells Prime In Vivo Alloreactive CD4 T Lymphocytes Toward Type 2 Cytokine- and TGF-β-Producing Cells in the Absence of CD8 T Cell Activation

The Journal of Immunology ◽

10.4049/jimmunol.165.9.4994 ◽

2000 ◽

Vol 165 (9) ◽

pp. 4994-5003 ◽

Cited By ~ 27

Author(s):

Gilles Foucras ◽

Jérôme D. Coudert ◽

Christiane Coureau ◽

Jean-Charles Guéry

Keyword(s):

Dendritic Cells ◽

T Cell ◽

T Lymphocytes ◽

T Cell Activation ◽

Cell Activation ◽

Cd8 T Cell

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Causes of T lymphocyte activation in HIV-infected patients coinfected with hepatitis C virus

Terapevticheskii arkhiv ◽

10.17116/terarkh2016881122-28 ◽

2016 ◽

Vol 88 (11) ◽

pp. 22-28

Author(s):

K V Shmagel ◽

N G Shmagel ◽

L B Korolevskaya ◽

E V Saydakova ◽

V A Chereshnev

Keyword(s):

T Cells ◽

Hepatitis C ◽

T Cell ◽

T Lymphocytes ◽

T Cell Activation ◽

T Lymphocyte ◽

Cell Activation ◽

Lymphocyte Activation ◽

Cd8 T Cell ◽

Cd8 T Lymphocytes

Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.

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Formation of a Unique Population of CD8+ T Lymphocytes after Adoptive Transfer of Syngeneic Splenocytes to Mice with Lymphopenia

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672921020137 ◽

2021 ◽

Author(s):

Yu. Yu. Silaeva ◽

A. A. Kalinina ◽

L. M. Khromykh ◽

A. V. Deykin ◽

D. B. Kazansky

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Chemokine Receptor ◽

Adoptive Transfer ◽

Memory T Cells ◽

Cd8 T Cell ◽

Surface Activation ◽

Cd8 T Lymphocytes ◽

First Time ◽

Donor Lymphocytes

Abstract Under conditions of lymphopenia, T lymphocytes proliferate and acquire a surface activation phenotype, which in many respects is similar to the phenotype of true memory T cells. We investigated the phenotypic features of the CD8+ T-cell population formed from donor lymphocytes after adoptive transfer of syngeneic splenocytes to sublethally irradiated mice. This population expresses markers CD44, CD122, CD5, CD49d and the chemokine receptor CXCR3. Thus, for the first time, the phenomenon of the formation of a population of T cells with signs of suppressive CD8+ T lymphocytes and true memory cells was demonstrated.

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