Detection, Expansion, and Isolation of Human MAIT Cells

TILs comprise functionally distinct conventional and unconventional T cell subsets and their role in responses to CRC treatments is poorly understood. We explored recovery of viable TILs from cryopreserved tumor biopsies of (chemo)-radiated patients with rectal cancer to establish a platform for retrospective TIL analyses of frozen tumors from pre-selected study cohorts. Frequencies of TIL subsets and their capacity to mount IFN-γ responses in cell suspensions of fresh vs. cryopreserved portions of the same tumor biopsies were determined for platform validation. The percentages and proportions of CD4+ TILs and CD8+ cytotoxic T lymphocytes (CTLs) among total TILs were not affected by cryopreservation. While recovery of unconventional γδ T cells and mucosal-associated invariant T cells (MAIT cells) was stable after cryopreservation, the regulatory T cells (Tregs) were reduced, but in sufficient yields for quantification. IFN-γ production by in vitro-stimulated CD4+ TILs, CTLs, γδ T cells, and MAIT cells were proportionally similar in fresh and cryopreserved tumor portions, albeit the latter displayed lower levels. Thus, the proposed platform intended for TIL analyses on cryopreserved tumor biobank biopsies holds promises for studies linking the quantity and quality of TIL subsets with specific clinical outcome after CRC treatment.

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Intrapulmonary vaccination with delta-inulin adjuvant stimulates non-polarised chemotactic signalling and diverse cellular interaction

Mucosal Immunology ◽

10.1038/s41385-021-00379-6 ◽

2021 ◽

Author(s):

Kia C. Ferrell ◽

Erica L. Stewart ◽

Claudio Counoupas ◽

Thomas M. Ashhurst ◽

Warwick J. Britton ◽

...

Keyword(s):

Γδ T Cells ◽

Mucosal Vaccine ◽

Cellular Interaction ◽

Respiratory Pathogens ◽

Preclinical Development ◽

Cell Recruitment ◽

Mait Cells ◽

Attractive Option ◽

Early Inflammatory Response ◽

Chemotactic Factors

AbstractThere is an urgent need for novel vaccination strategies to combat respiratory pathogens. Mucosal vaccine delivery is an attractive option as it directly targets the site of infection; however, preclinical development has been hindered by a lack of suitable mucosal adjuvants and a limited understanding of their immune effects in the lung environment. Herein, we define the early immune events following the intrapulmonary delivery of a vaccine incorporating the adjuvant delta-inulin. Analysis of the early inflammatory response showed vaccine-induced innate cell recruitment to lungs and local lymph nodes (LN) was transient and non-polarised, correlating with an increase in pulmonary chemotactic factors. Use of fluorescently labelled adjuvant revealed widespread tissue dissemination of adjuvant particles, coupled with broad cellular uptake and transit to the lung-draining LN by a range of innate immune cells. Mass cytometric analysis revealed extensive phenotypic changes in innate and adaptive cell subsets induced by vaccination; this included identification of unconventional lymphocytes such as γδ-T cells and MAIT cells that increased following vaccination and displayed an activated phenotype. This study details a comprehensive view of the immune response to intrapulmonary adjuvant administration and provides pre-clinical evidence to support delta-inulin as a suitable adjuvant for pulmonary vaccines.

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MAIT cells (TCR7.2+CD161++CD8+) are functionally impaired during chronic SHIV infection

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2020.09.752 ◽

2020 ◽

Vol 101 ◽

pp. 288

Author(s):

A. Murugesan ◽

C. Ibegbu ◽

T. Styles ◽

S. Hicks ◽

P. Reddy ◽

...

Keyword(s):

Mait Cells ◽

Functionally Impaired ◽

Shiv Infection

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The role of unconventional T cells in COVID-19

Irish Journal of Medical Science (1971 -) ◽

10.1007/s11845-021-02653-9 ◽

2021 ◽

Author(s):

Kristen Orumaa ◽

Margaret R. Dunne

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Treatment Strategies ◽

Γδ T Cells ◽

Protective Role ◽

T Cell Subsets ◽

Viral Immunity ◽

Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

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Regulation and Functions of Protumoral Unconventional T Cells in Solid Tumors

Cancers ◽

10.3390/cancers13143578 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3578

Author(s):

Emilie Barsac ◽

Carolina de Amat Herbozo ◽

Loïc Gonzalez ◽

Thomas Baranek ◽

Thierry Mallevaey ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Immunity ◽

Cell Biology ◽

Therapeutic Potential ◽

Γδ T Cells ◽

Feasibility Studies ◽

T Cell Subsets ◽

Mait Cells ◽

Nonpeptide Antigens

The vast majority of studies on T cell biology in tumor immunity have focused on peptide-reactive conventional T cells that are restricted to polymorphic major histocompatibility complex molecules. However, emerging evidence indicated that unconventional T cells, including γδ T cells, natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells are also involved in tumor immunity. Unconventional T cells span the innate–adaptive continuum and possess the unique ability to rapidly react to nonpeptide antigens via their conserved T cell receptors (TCRs) and/or to activating cytokines to orchestrate many aspects of the immune response. Since unconventional T cell lineages comprise discrete functional subsets, they can mediate both anti- and protumoral activities. Here, we review the current understanding of the functions and regulatory mechanisms of protumoral unconventional T cell subsets in the tumor environment. We also discuss the therapeutic potential of these deleterious subsets in solid cancers and why further feasibility studies are warranted.

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