CD8 and CD4 T Cell Populations in Human Kidneys

Background: At border sites, and in internal organs, tissue resident memory T cells (TRM) 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 IFNγ than circulating cells and were frequently polyfunctional. Conclusion: Functional T cells with the characteristic traits of TRM reside in human kidney tissues. These cells are more often actively cycling and frequently express CXCR3 and CXCR6.

[1]  T. Kuhlmann,et al.  Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions. , 2020, Brain : a journal of neurology.

[2]  J. Harty,et al.  Peripherally induced brain tissue-resident memory CD8+ T cells mediate protection against CNS infection , 2020, Nature Immunology.

[3]  E. Remmerswaal,et al.  Tissue‐resident mucosal‐associated invariant T (MAIT) cells in the human kidney represent a functionally distinct subset , 2020, European journal of immunology.

[4]  J. Paul Robinson,et al.  Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition) , 2019, European journal of immunology.

[5]  Kouji Matsushima,et al.  CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways , 2019, The Journal of experimental medicine.

[6]  K. Beagley,et al.  Human Tissue-Resident Mucosal-Associated Invariant T (MAIT) Cells in Renal Fibrosis and CKD. , 2019, Journal of the American Society of Nephrology : JASN.

[7]  F. Claas,et al.  Characterization of donor and recipient CD8+ tissue-resident memory T cells in transplant nephrectomies , 2019, Scientific Reports.

[8]  D. Masopust,et al.  Tissue-Resident T Cells and Other Resident Leukocytes. , 2019, Annual review of immunology.

[9]  E. Remmerswaal,et al.  Tissue-resident memory T cells populate the human brain , 2018, Nature Communications.

[10]  A. Ertel,et al.  The Chemokine Receptor CXCR3 Promotes CD8+ T Cell Accumulation in Uninfected Salivary Glands but Is Not Necessary after Murine Cytomegalovirus Infection , 2018, The Journal of Immunology.

[11]  Scott N. Mueller,et al.  Chemokine Receptor–Dependent Control of Skin Tissue–Resident Memory T Cell Formation , 2017, The Journal of Immunology.

[12]  Yufeng Shen,et al.  Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. , 2017, Cell reports.

[13]  N. Kootstra,et al.  Human intrahepatic CD69 + CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity , 2017, Scientific Reports.

[14]  Leo Swadling,et al.  IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection , 2017, The Journal of experimental medicine.

[15]  H. Clevers,et al.  Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells , 2016, Nature Immunology.

[16]  M. Feltkamp,et al.  Clinically Relevant Reactivation of Polyomavirus BK (BKPyV) in HLA-A02-Positive Renal Transplant Recipients Is Associated with Impaired Effector-Memory Differentiation of BKPyV-Specific CD8+ T Cells , 2016, PLoS pathogens.

[17]  W. Shi,et al.  Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes , 2016, Science.

[18]  H. Pircher,et al.  Infection History Determines the Differentiation State of Human CD8+ T Cells , 2015, Journal of Virology.

[19]  Yufeng Shen,et al.  Spatial Map of Human T Cell Compartmentalization and Maintenance over Decades of Life , 2014, Cell.

[20]  Andrea J. Radtke,et al.  The chemokine receptor CXCR6 is required for the maintenance of liver memory CD8⁺ T cells specific for infectious pathogens. , 2014, The Journal of infectious diseases.

[21]  M. Sykes,et al.  Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. , 2013, Immunity.

[22]  A. Singer,et al.  IL-7 signaling must be intermittent, not continuous, during CD8 T cell homeostasis to promote cell survival instead of cell death , 2012, Nature Immunology.

[23]  E. Remmerswaal,et al.  Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes. , 2012, Blood.

[24]  E. Remmerswaal,et al.  CD8⁺ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung. , 2011, The Journal of clinical investigation.

[25]  Ronald N Germain,et al.  L-selectin-negative CCR7− effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells , 2007, Nature Immunology.

[26]  Pedro Romero,et al.  Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes1 , 2007, The Journal of Immunology.

[27]  R. Koup,et al.  Intracellular cytokine optimization and standard operating procedure , 2006, Nature Protocols.

[28]  R. Clark,et al.  Response to Comment on “The Vast Majority of CLA+ T Cells Are Resident in Normal Skin” , 2006, The Journal of Immunology.

[29]  Corey M. Carlson,et al.  Kruppel-like factor 2 regulates thymocyte and T-cell migration , 2006, Nature.

[30]  E. Remmerswaal,et al.  IL-7 receptor alpha chain expression distinguishes functional subsets of virus-specific human CD8+ T cells. , 2005, Blood.

[31]  Lisa M. Ebert,et al.  A Skin-selective Homing Mechanism for Human Immune Surveillance T Cells , 2004, The Journal of experimental medicine.

[32]  Laurie H Glimcher,et al.  A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment , 2000, Cell.

[33]  E. Remmerswaal,et al.  UvA-DARE ( Digital Academic Repository ) CD 8 ( + ) T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung , 2011 .

[34]  S. Szabo,et al.  Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. , 2002, Science.

[35]  James J. Campbell,et al.  Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes. , 2002, The American journal of pathology.