NOD Mice Are Functionally Deficient in the Capacity of Cross-presentation

Overview

Journal Immunol Cell Biol

Publisher Wiley

Specialties Allergy & Immunology
Cell Biology

Date 2015 Jan 21

PMID 25601275

Citations 6

Authors

Chin-Nien Lee

Andrew M Lew

Ken Shortman

Li Wu

Affiliations

Soon will be listed here.

Abstract

Cross-presentation by CD8(+) conventional dendritic cells (cDCs) is involved in the maintenance of peripheral tolerance and this process is termed cross-tolerance. Previous reports showed that non-obese diabetic (NOD) mice have reduced number of splenic CD8(+) cDCs compared with non-diabetic strains, and that the administration of Flt3L to enhance DC development resulted in reduced diabetes incidence. As CD8(+) cDCs are the most efficient antigen cross-presenting cells, it was assumed that reduced cross-presentation by non-activated, tolerogenic CD8(+) cDC predisposes to autoimmune diabetogenesis. Here we show for the first time that indeed NOD mice have a defect in autoantigen cross-presentation capacity. First, we showed that NOD CD8(+) cDCs were less sensitive to iatrogenic cytochrome c, which had previously been shown to selectively deplete CD8(+) cDCs that functionally cross-present. Second, we found that proliferation of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific CD8(+) T cells was impaired in NOD compared with non-obese diabetes resistant mice after immunization with cell associated recombinant fusion protein containing the cognate IGRP peptide. This study, therefore, suggests that the reduced number of CD8(+) cDCs in NOD mice, coupled with the reduced capacity to cross-present self-antigens, reduces the overall capacity to maintain peripheral tolerance in the spontaneous autoimmune type 1 diabetes mice.

Citing Articles

WDFY4 deficiency in NOD mice ameliorates autoimmune diabetes and insulitis.

Ferris S, Liu T, Chen J, Ohara R, Ou F, Wu R Proc Natl Acad Sci U S A. 2023; 120(13):e2219956120.

PMID: 36940342 PMC: 10068798. DOI: 10.1073/pnas.2219956120.

Development and Characterization of a Preclinical Model for the Evaluation of CD205-Mediated Antigen Delivery Therapeutics in Type 1 Diabetes.

Schloss J, Ali R, Babad J, Guerrero-Ros I, Pongsachai J, He L Immunohorizons. 2019; 3(6):236-253.

PMID: 31356169 PMC: 6668927. DOI: 10.4049/immunohorizons.1900014.

Altered Function of Antigen-Presenting Cells in Type 1 Diabetes: A Challenge for Antigen-Specific Immunotherapy?.

Creusot R, Postigo-Fernandez J, Teteloshvili N Diabetes. 2018; 67(8):1481-1494.

PMID: 30030289 PMC: 6054431. DOI: 10.2337/db17-1564.

The Importance of Dendritic Cells in Maintaining Immune Tolerance.

Audiger C, Rahman M, Yun T, Tarbell K, Lesage S J Immunol. 2017; 198(6):2223-2231.

PMID: 28264998 PMC: 5343761. DOI: 10.4049/jimmunol.1601629.

Influenza H3N2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in CAST/EiJ mice.

Leist S, Pilzner C, van den Brand J, Dengler L, Geffers R, Kuiken T BMC Genomics. 2016; 17:143.

PMID: 26921172 PMC: 4769537. DOI: 10.1186/s12864-016-2483-y.

References

Poulton L, Smyth M, Hawke C, Silveira P, Shepherd D, Naidenko O . Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice. Int Immunol. 2001; 13(7):887-96. DOI: 10.1093/intimm/13.7.887. View

Heath W, Belz G, Behrens G, Smith C, Forehan S, Parish I . Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev. 2004; 199:9-26. DOI: 10.1111/j.0105-2896.2004.00142.x. View

Santamaria P, Utsugi T, Park B, Averill N, Kawazu S, Yoon J . Beta-cell-cytotoxic CD8+ T cells from nonobese diabetic mice use highly homologous T cell receptor alpha-chain CDR3 sequences. J Immunol. 1995; 154(5):2494-503. View

Bevan M . Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med. 1976; 143(5):1283-8. PMC: 2190184. DOI: 10.1084/jem.143.5.1283. View

Wilson N, El-Sukkari D, Belz G, Smith C, Steptoe R, Heath W . Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood. 2003; 102(6):2187-94. DOI: 10.1182/blood-2003-02-0513. View

Clare-Salzler M, Brooks J, Chai A, van Herle K, Anderson C . Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. J Clin Invest. 1992; 90(3):741-8. PMC: 329925. DOI: 10.1172/JCI115946. View

Lin M, Zhan Y, Proietto A, Prato S, Wu L, Heath W . Selective suicide of cross-presenting CD8+ dendritic cells by cytochrome c injection shows functional heterogeneity within this subset. Proc Natl Acad Sci U S A. 2008; 105(8):3029-34. PMC: 2268579. DOI: 10.1073/pnas.0712394105. View

Rodriguez A, Regnault A, Kleijmeer M, Ricciardi-Castagnoli P, Amigorena S . Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol. 1999; 1(6):362-8. DOI: 10.1038/14058. View

Lee C, Lew A, Wu L . The potential role of dendritic cells in the therapy of Type 1 diabetes. Immunotherapy. 2013; 5(6):591-606. DOI: 10.2217/imt.13.48. View

10.

Proietto A, van Dommelen S, Zhou P, Rizzitelli A, DAmico A, Steptoe R . Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc Natl Acad Sci U S A. 2008; 105(50):19869-74. PMC: 2604962. DOI: 10.1073/pnas.0810268105. View

11.

Ogasawara K, Hamerman J, Hsin H, Chikuma S, Bour-Jordan H, Chen T . Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity. 2003; 18(1):41-51. DOI: 10.1016/s1074-7613(02)00505-8. View

12.

Heath W, Carbone F . Cross-presentation in viral immunity and self-tolerance. Nat Rev Immunol. 2002; 1(2):126-34. DOI: 10.1038/35100512. View

13.

Zhan Y, Carrington E, Van Nieuwenhuijze A, Bedoui S, Seah S, Xu Y . GM-CSF increases cross-presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells. Eur J Immunol. 2011; 41(9):2585-95. DOI: 10.1002/eji.201141540. View

14.

Marino E, Tan B, Binge L, Mackay C, Grey S . B-cell cross-presentation of autologous antigen precipitates diabetes. Diabetes. 2012; 61(11):2893-905. PMC: 3478535. DOI: 10.2337/db12-0006. View

15.

Belz G, Nutt S . Transcriptional programming of the dendritic cell network. Nat Rev Immunol. 2012; 12(2):101-13. DOI: 10.1038/nri3149. View

16.

Qiu C, Miyake Y, Kaise H, Kitamura H, Ohara O, Tanaka M . Novel subset of CD8{alpha}+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens. J Immunol. 2009; 182(7):4127-36. DOI: 10.4049/jimmunol.0803364. View

17.

Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig M, Steinman R . Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med. 2002; 196(12):1627-38. PMC: 2196060. DOI: 10.1084/jem.20021598. View

18.

Shortman K, Heath W . The CD8+ dendritic cell subset. Immunol Rev. 2010; 234(1):18-31. DOI: 10.1111/j.0105-2896.2009.00870.x. View

19.

Luckashenak N, Schroeder S, Endt K, Schmidt D, Mahnke K, Bachmann M . Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivo. Immunity. 2008; 28(4):521-32. DOI: 10.1016/j.immuni.2008.02.018. View

20.

Kurts C, Kosaka H, Carbone F, Miller J, Heath W . Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8(+) T cells. J Exp Med. 1997; 186(2):239-45. PMC: 2198972. DOI: 10.1084/jem.186.2.239. View