Dataset Information

Identification of resident memory CD8⁺ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue.

ABSTRACT: Cross-reactive CD4⁺ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2–reactive CD8⁺ T cells. However, large numbers of memory CD8⁺ T cells reside in tissues, feasibly harboring localized SARS-CoV-2–specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19 (coronavirus disease 2019). We found that SARS-CoV-2–specific memory CD4⁺ T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2–specific memory CD8⁺ T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2–specific memory CD8⁺ T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus–specific memory CD8⁺ T cells, but were functionally less potent than other virus-specific memory CD8⁺ T cell responses. The presence of preexisting tissue-resident memory CD8⁺ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.

SUBMITTER: Niessl J

PROVIDER: S-EPMC10763663 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue.

Niessl Julia J Sekine Takuya T Lange Joshua J Konya Viktoria V Forkel Marianne M Maric Jovana J Rao Anna A Mazzurana Luca L Kokkinou Efthymia E Weigel Whitney W Llewellyn-Lacey Sian S Hodcroft Emma B EB Karlsson Annika C AC Fehrm Johan J Sundman Joar J Price David A DA Mjösberg Jenny J Friberg Danielle D Buggert Marcus M

Science immunology 20211022 64

Cross-reactive CD4+ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2–reactive CD8+ T cells. However, large numbers of memory CD8+ T cells reside in tissues, feasibly harboring localized SARS-CoV-2–specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cell ...[more]

PMID: 34519539

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Project description:IntroductionDespite recent advances in immunotherapy for hepatocellular carcinoma (HCC), the overall modest response rate underscores the need for a better understanding of the tumor microenvironment (TME) of HCC. We have previously shown that CD38 is widely expressed on tumor-infiltrating leukocytes (TILs), predominantly on CD3+ T cells and monocytes. However, its specific role in the HCC TME remains unclear.MethodsIn this current study, we used cytometry time-of-flight (CyTOF), bulk RNA sequencing on sorted T cells, and single-cell RNA (scRNA) sequencing to interrogate expression of CD38 and its correlation with T cell exhaustion in HCC samples. We also employed multiplex immunohistochemistry (mIHC) for validating our findings.ResultsFrom CyTOF analysis, we compared the immune composition of CD38-expressing leukocytes in TILs, non-tumor tissue-infiltrating leukocytes (NIL), and peripheral blood mononuclear cells (PBMC). We identified CD8+ T cells as the dominant CD38-expressing TILs and found that CD38 expression was significantly higher in CD8+ TRM in TILs than in NILs. Furthermore, through transcriptomic analysis on sorted CD8+ TRM from HCC tumors, we observed a higher expression of CD38 along with T cell exhaustion genes, including PDCD1 and CTLA4, compared to the circulating memory CD8 T cells from PBMC. This was validated by scRNA sequencing that revealed co-expression of CD38 with PDCD1, CTLA4, and ITGAE (CD103) in T cells from HCC tumors. The protein co-expression of CD38 and PD-1 on CD8+ T cells was further demonstrated by mIHC on HCC FFPE tissues, marking CD38 as a T cell co-exhaustion marker in HCC. Lastly, the higher proportions of CD38+PD-1+ CD8+ T cells and CD38+PD-1+ TRM were significantly associated with the higher histopathological grades of HCC, indicating its role in the aggressiveness of the disease.ConclusionTaken together, the concurrent expression of CD38 with exhaustion markers on CD8+ TRM underpins its role as a key marker of T cell exhaustion and a potential therapeutic target for restoring cytotoxic T cell function in HCC.

Dataset Information

Identification of resident memory CD8⁺ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue.

Publications

Identification of resident memory CD8<sup>+</sup> T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue.

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