scholarly journals Human γδ T cells recognize CD1b by two distinct mechanisms

2020 ◽  
Vol 117 (37) ◽  
pp. 22944-22952 ◽  
Author(s):  
Josephine F. Reijneveld ◽  
Tonatiuh A. Ocampo ◽  
Adam Shahine ◽  
Benjamin S. Gully ◽  
Pierre Vantourout ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Dual Reactivity ◽  
Lipid Antigens ◽  
Cellular Immune System ◽  
Lipid Antigen ◽  
Multiple Donors ◽  
Cellular Immune ◽  
Antigen Presenting ◽  
Peptide Display

γδ T cells form an abundant part of the human cellular immune system, where they respond to tissue damage, infection, and cancer. The spectrum of known molecular targets recognized by Vδ1-expressing γδ T cells is becoming increasingly diverse. Here we describe human γδ T cells that recognize CD1b, a lipid antigen-presenting molecule, which is inducibly expressed on monocytes and dendritic cells. Using CD1b tetramers to study multiple donors, we found that many CD1b-specific γδ T cells use Vδ1. Despite their common use of Vδ1, three CD1b-specific γδ T cell receptors (TCRs) showed clear differences in the surface of CD1b recognized, the requirement for lipid antigens, and corecognition of butryophilin-like proteins. Several Vγ segments were present among the CD1b-specific TCRs, but chain swap experiments demonstrated that CD1b specificity was mediated by the Vδ1 chain. One of the CD1b-specific Vδ1+ TCRs paired with Vγ4 and shows dual reactivity to CD1b and butyrophilin-like proteins. αβ TCRs typically recognize the peptide display platform of MHC proteins. In contrast, our results demonstrate the use of rearranged receptors to mediate diverse modes of recognition across the surface of CD1b in ways that do and do not require carried lipids.

Evidence for a role of γδ T cells in demyelinating diseases as determined by activation states and responses to lipid antigens

2000 ◽  
Vol 107 (2) ◽  
pp. 124-129 ◽  
Author(s):  
G Borsellino ◽  
O Koul ◽  
R Placido ◽  
D Tramonti ◽  
S Luchetti ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Demyelinating Diseases ◽  
Lipid Antigens

scholarly journals The analysis of the long-term impact of SARS-CoV-2 on the cellular immune system in individuals recovering from COVID-19 reveals a profound NKT cell impairment

2020 ◽  
Author(s):  
jia liu ◽  
Xuecheng Yang ◽  
Hua Wang ◽  
Ziwei Li ◽  
Hui Deng ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Annexin V ◽  
Double Positive ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune System ◽  
Cellular Immune

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects millions of people and killed hundred-thousands of individuals. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remained to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19 convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2 unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of Annexin V and 7-AAD double positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies, TIM-3 expression on CD4 and CD8 T cells, as well as PD-L1 expression on B cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by GzmB expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully capable to proliferate and produce effector cytokines upon TCR stimulation. Collectively, we provide the first comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.

scholarly journals Evaluation of Feline Monocyte-Derived Dendritic Cells Loaded with Internally Inactivated Virus as a Vaccine against Feline Immunodeficiency Virus

2008 ◽  
Vol 15 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Giulia Freer ◽  
Donatella Matteucci ◽  
Paola Mazzetti ◽  
Francesca Tarabella ◽  
Valentina Catalucci ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Functions ◽  
Peripheral Blood Mononuclear ◽  
Challenge Virus ◽  
Homologous Virus ◽  
Antibody Titers ◽  
Cellular Immune ◽  
Antigen Presenting

ABSTRACT Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4+/CD8+ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.

Antigens and Antigen-Presenting Molecules for γδ T Cells

1991 ◽  
pp. 229-234 ◽  
Author(s):  
H. Band ◽  
St. A. Porcelli ◽  
G. Panchamoorthy ◽  
J. Mclean ◽  
C. T. Morita ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Antigen Presenting

scholarly journals Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a

2016 ◽  
Vol 213 (11) ◽  
pp. 2399-2412 ◽  
Author(s):  
Ka Lun Cheung ◽  
Rachael Jarrett ◽  
Sumithra Subramaniam ◽  
Maryam Salimi ◽  
Danuta Gutowska-Owsiak ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Therapeutic Potential ◽  
T Helper ◽  
T Helper 17 ◽  
Lipid Antigens ◽  
T Cell Antigens ◽  
Cell Release ◽  
Antigen Presenting ◽  
Psoriatic Lesions

Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. In this study, we observed expression of a cytoplasmic PLA2 (PLA2G4D) in psoriatic mast cells but, unexpectedly, also found PLA2G4D activity to be extracellular. This was explained by IFN-α–induced mast cell release of exosomes, which transferred cytoplasmic PLA2 activity to neighboring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid-specific CD1a-reactive T cells inducing production of IL-22 and IL-17A. Circulating and skin-derived T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared with healthy controls. Overall, these data present an alternative model of psoriasis pathogenesis in which lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA2 inhibition or CD1a blockade may have therapeutic potential for psoriasis.

scholarly journals Thymic Presentation of Autoantigens and the Efficiency of Negative Selection

2003 ◽  
Vol 5 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Hugo A. van den Berg ◽  
Carmen Molina-París
Keyword(s):  
T Cells ◽  
Negative Selection ◽  
Genetic Recombination ◽  
T Cell Repertoire ◽  
Antigen Receptors ◽  
Tolerance Mechanisms ◽  
Cell Repertoire ◽  
Cellular Immune System ◽  
Cellular Immune ◽  
The Impact

Antigen recognition by the adaptive cellular immune system is based on a diverse repertoire of antigen receptors. Since this repertoire is formed by genetic recombination, a number of receptors are autoreactive by chance, giving rise to the threat of autoimmune disease. Potentially autoreactive T lymphocytes (T cells) are rendered ineffective by various tolerance mechanisms. One of these mechanisms is negative selection, the deletion from the repertoire of immature autoreactive T cells in the thymus. The present paper shows how to assess the contribution made by negative selection relative to other tolerisation mechanisms by deducing the impact of negative selection on the T cell repertoire from the statistics of autoantigen presentation in the thymus.

Rapid Ex Vivo Expansion of CMV Specific CTL Suitable for Clinical Immunotherapy Using CpG-DNA Matured PBMC Infected with Recombinant MVA.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5102-5102
Author(s):  
Don J. Diamond ◽  
Zhongde Wang ◽  
Simon F. Lacey ◽  
Corinna La Rosa
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Attractive Alternative ◽  
Memory Cd8 T Cells ◽  
Equal Importance ◽  
High Level ◽  
Cellular Immune ◽  
Antigen Presenting

Abstract Adoptive transfer of ex vivo expanded CMV-specific T cells is an effective approach, and an attractive alternative to using anti-virals to manage CMV infection for HSCT recipients. We recently published a robust approach to expanding CMV-specific CTL based on infection of autologous EBV-LCL with the attenuated poxvirus, Modified Vaccinia Ankara (MVA), expressing CMV pp65, pp150, and IE1 proteins. This approach causes vigorous, up to 500fold expansions in as little as 12–14 days of memory CD8+ T cells specific for these immunodominant antigens. In order to improve the specificity of the expanded T cells, a method was sought to derive effective antigen presenting cells (APC) that avoided the use of EBV-LCL. Of equal importance is to develop an expansion approach that avoids the need to involve virally infected APC in developing a clinical product. Our preliminary observation is that rMVA can infect PBMC in vitro, causing high levels of expression of recombinant CMV antigens. To be permissible for high level expression from rMVA, fresh PBMC were treated with different combinations of single-stranded CpG-containing phosphorothioate backbone oligonucleotides (ODN). A three-day incubation with a combination of two ODN (ODN # 2006 and 2216) which are known to stimulate both plasmacytoid dendritic and B-cells were found to reproducibly generate a highly rMVA infectable population of PBMC. In all five healthy CMV-positive donors tested, CpG ODN treated autologous PBMC, infected with recombinant rMVA, elicited a 20-fold average expansion of CMV-specific CD8+ T cells, in 10 days. Several different rMVA expressing CMV genes were evaluated, including a novel vector expressing the UL44 gene product, an immunodominant target of the host cellular immune response. The expanded T cell populations showed minimal alloreactivity, and exhibited high levels of CMV-specific MHC Class I tetramer binding, epitope-specific cytokine production, and cytotoxic activity. The availability of a source of autologous professional APC that can be used after only 3 days of priming, enhances the attractiveness of using rMVA for adoptive immunotherapy for HSCT recipients or donor vaccination.

scholarly journals The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies

2015 ◽  
Vol 5 (4) ◽  
pp. e306-e306 ◽  
Author(s):  
T Dosani ◽  
M Carlsten ◽  
I Maric ◽  
O Landgren
Keyword(s):  
T Cells ◽  
Immune System ◽  
Natural Killer ◽  
Γδ T Cells ◽  
Tumor Evolution ◽  
The Status ◽  
And Function ◽  
Cellular Immune ◽  
Functional Profiles ◽  
Killer T Cells

Abstract As vast strides are being made in the management and treatment of multiple myeloma (MM), recent interests are increasingly focusing on understanding the development of the disease. The knowledge that MM develops exclusively from a protracted phase of monoclonal gammopathy of undetermined significance provides an opportunity to study tumor evolution in this process. Although the immune system has been implicated in the development of MM, the scientific literature on the role and status of various immune components in this process is broad and sometimes contradictory. Accordingly, we present a review of cellular immune subsets in myelomagenesis. We summarize the current literature on the quantitative and functional profiles of natural killer cells and T-cells, including conventional T-cells, natural killer T-cells, γδ T-cells and regulatory T-cells, in myelomagenesis. Our goal is to provide an overview of the status and function of these immune cells in both the peripheral blood and the bone marrow during myelomagenesis. This provides a better understanding of the nature of the immune system in tumor evolution, the knowledge of which is especially significant considering that immunotherapies are increasingly being explored in the treatment of both MM and its precursor conditions.

scholarly journals Enterobacteria‐Infected T Cells as Antigen‐Presenting Cells for Cytotoxic CD8 T Cells: A Contribution to the Self‐Limitation of Cellular Immune Reactions in Reactive Arthritis?

1997 ◽  
Vol 175 (5) ◽  
pp. 1121-1127 ◽  
Author(s):  
Birgit Ackermann ◽  
Martin S. Staege ◽  
Angelika B. Reske‐Kunz ◽  
Hans‐Peter Dienes ◽  
Karl‐Hermann Meyer zum Büschenfelde ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Reactive Arthritis ◽  
Antigen Presenting Cells ◽  
The Self ◽  
Immune Reactions ◽  
Cellular Immune ◽  
Antigen Presenting
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