Dataset Information

CD8 and CD4 T Cell Populations in Human Kidneys.

ABSTRACT:

Background

At border sites, and in internal organs, tissue resident memory T cells (T_RM) contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However, information on the presence and function of these cells in the human kidney is scant. In order to better understand the T cell-mediated immunological defense in this organ, we aimed to determine phenotypic and functional aspects of CD8 and CD4 T cells present in healthy and allograft kidney tissue.

Methods

Using multichannel flow cytometry, we assessed the phenotype and function of T cells in healthy renal tissue samples (n = 5) and kidney allograft tissue (n = 7) and compared these aspects to T cells in peripheral blood from healthy controls (n = 13).

Results

Kidney tissue samples contained substantial amounts of CD8 and CD4 T cells. In contrast to the circulating cells, kidney T cells frequently expressed CD69 and CD103, and were more often actively cycling. Furthermore, nearly all kidney T cells expressed CXCR3, and often expressed CXCR6 compared to T cells in the circulation. Markedly, kidney T cells produced greater quantities of IFN? than circulating cells and were frequently polyfunctional.

Conclusion

Functional T cells with the characteristic traits of T_RM reside in human kidney tissues. These cells are more often actively cycling and frequently express CXCR3 and CXCR6.

SUBMITTER: van der Putten C

PROVIDER: S-EPMC7912772 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

CD8 and CD4 T Cell Populations in Human Kidneys.

van der Putten Carlos C Remmerswaal Ester B M EBM Terpstra Matty L ML van der Bom Nelly D ND Kers Jesper J Ten Berge Ineke J M IJM Geerlings Suzanne E SE van Lier René A W RAW Bemelman Frederike J FJ van Aalderen Michiel C MC

Cells 20210201 2

<h4>Background</h4>At border sites, and in internal organs, tissue resident memory T cells (T<sub>RM)</sub> contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However, information on the presence and function of these cells in the human kidney is scant. In order to better understand the T cell-mediated immunological defense in this organ, we aimed to determine phenotypic and functional aspects of CD8 and CD4 T cells present in healthy and allograft kidn ...[more]

PMID: 33535505

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Project description:BackgroundPrediction of T cell immunogenicity is a topic of considerable interest, both in terms of basic understanding of the mechanisms of T cells responses and in terms of practical applications. HLA binding affinity is often used to predict T cell epitopes, since HLA binding affinity is a key requisite for human T cell immunogenicity. However, immunogenicity at the population it is complicated by the high level of variability of HLA molecules, potential other factors beyond HLA as well as the frequent lack of HLA typing data. To overcome those issues, we explored an alternative approach to identify the common characteristics able to distinguish immunogenic peptides from non-recognized peptides.MethodsSets of dominant epitopes derived from peer-reviewed published papers were used in conjunction with negative peptides from the same experiments/donors to train neural networks and generate an "immunogenicity score." We also compared the performance of the immunogenicity score with previously described method for immunogenicity prediction based on HLA class II binding at the population level.ResultsThe immunogenicity score was validated on a series of independent datasets derived from the published literature, representing 57 independent studies where immunogenicity in human populations was assessed by testing overlapping peptides spanning different antigens. Overall, these testing datasets corresponded to over 2,000 peptides and tested in over 1,600 different human donors. The 7-allele method prediction and the immunogenicity score were associated with similar performance [average area under the ROC curve (AUC) values of 0.703 and 0.702, respectively] while the combined methods reached an average AUC of 0.725. This increase in average AUC value is significant compared with the immunogenicity score (p = 0.0135) and a strong trend toward significance is observed when compared to the 7-allele method (p = 0.0938). The new immunogenicity score method is now freely available using CD4 T cell immunogenicity prediction tool on the Immune Epitope Database website (http://tools.iedb.org/CD4episcore).ConclusionThe new immunogenicity score predicts CD4 T cell immunogenicity at the population level starting from protein sequences and with no need for HLA typing. Its efficacy has been validated in the context of different antigen sources, ethnicities, and disparate techniques for epitope identification.

Dataset Information

CD8 and CD4 T Cell Populations in Human Kidneys.

Background

Methods

Results

Conclusion

Publications

CD8 and CD4 T Cell Populations in Human Kidneys.

Similar Datasets

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