Increased islet antigen–specific regulatory and effector CD4 + T cells in healthy individuals with the type 1 diabetes–protective haplotype
Open accessAbstract
The DR1501-DQ6 haplotype confers protection against type 1 diabetes through islet-specific T regs and IL-10–producing T effs .
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Liu, W., Putnam, A. L., Xu-yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St. Groth, B. F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060772 · Cited by 2,606 · see citing works
HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus
Todd, J. A., Bell, J. I., & McDevitt, H. O. (1987) · Nature · doi:10.1038/329599a0 · Cited by 2,046 · see citing works
Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S. I., Nanan, R., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060468 · Cited by 1,512 · see citing works
Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., & Shevach, E. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904028 · Cited by 1,382 · see citing works
In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes
Tang, Q., Henriksen, K., Bi, M., Finger, E. B., Szot, G. L., Ye, J., Masteller, E. L., McDevitt, H. O., Bonyhadi, M. L., & Bluestone, J. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040139 · Cited by 1,219 · see citing works
Type 1 diabetes immunotherapy using polyclonal regulatory T cells
Bluestone, J. A., Buckner, J. H., Fitch, M., Gitelman, S. E., Gupta, S., Hellerstein, M. K., Herold, K. C., Lares, A., Lee, M. R., Li, K., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad4134 · Cited by 1,033 · see citing works
Defective Suppressor Function in CD4+CD25+ T-Cells From Patients With Type 1 Diabetes
Sm, L., Dayan, C. M., Bishop, A. J., Roep, B. O., Peakman, M., & Tree, T. I. M. (2005) · Diabetes · doi:10.2337/diabetes.54.1.92 · Cited by 861 · see citing works
HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Erlich, H., Valdes, A. M., Noble, J., Carlson, J. A., Varney, M., Concannon, P., Mychaleckyj, J. C., Todd, J. A., Bonella, P., Fear, A. L., et al. (2008) · Diabetes · doi:10.2337/db07-1331 · Cited by 790 · see citing works
Environmental risk factors for type 1 diabetes
Rewers, M., & Ludvigsson, J. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30507-4 · Cited by 676 · see citing works
tTregs, pTregs, and iTregs: similarities and differences
Shevach, E. M., & Thornton, A. M. (2014) · Immunological Reviews · doi:10.1111/imr.12160 · Cited by 609 · see citing works
Genetic risk factors for type 1 diabetes
Pociot, F., & Lernmark, Å. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30582-7 · Cited by 553 · see citing works
Noble, J. A., Valdes, A. M., Cook, M., Klitz, W., Thomson, G., & Erlich, H. A. (1996) · PubMed Central · Cited by 481 · see citing works
Stable inhibitory activity of regulatory T cells requires the transcription factor Helios
Kim, H.-J., Barnitz, R. A., Kreslavsky, T., Brown, F. D., Moffett, H., Lemieux, M. E., Kaygusuz, Y., Meissner, T., Holderried, T. A. W., Chan, S., et al. (2015) · Science · doi:10.1126/science.aad0616 · Cited by 441 · see citing works
Functional Defects and the Influence of Age on the Frequency of CD4+CD25+ T-Cells in Type 1 Diabetes
Brusko, T. M., Wasserfall, C. H., Clare-Salzler, M. J., Schatz, D., & Atkinson, M. A. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1407 · Cited by 398 · see citing works
Autoreactive T Cells in Healthy Individuals
Danke, N. A., Koelle, D. M., Yee, C., Beheray, S., & Kwok, W. W. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.10.5967 · Cited by 377 · see citing works
Self-citationNovak, E. J., Liu, A. W., Nepom, G. T., & Kwok, W. W. (1999) · Journal of Clinical Investigation · doi:10.1172/jci8476 · Cited by 376 · see citing works
Self-citationAnalysis of HLA-DQ Genotypes and Susceptibility in Insulin-Dependent Diabetes Mellitus
Baisch, J. M., Weeks, T., Giles, R. C., Hoover, M. L., Šťastný, P., & Capra, J. D. (1990) · New England Journal of Medicine · doi:10.1056/nejm199006283222602 · Cited by 332 · see citing works
Regulatory T Cell Specificity Directs Tolerance versus Allergy against Aeroantigens in Humans
Bacher, P., Heinrich, F., Stervbo, U., Nienen, M., Vahldieck, M., Iwert, C., Vogt, K., Kollet, J., Babel, N., Sawitzki, B., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.050 · Cited by 319 · see citing works
Schneider, A., Rieck, M., Sanda, S., Pihoker, C., Greenbaum, C. J., & Buckner, J. H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.7350 · Cited by 303 · see citing works
Babon, J. A. B., DeNicola, M., Blodgett, D. M., Crèvecoeur, I., Buttrick, T., Maehr, R., Bottino, R., Naji, A., Kaddis, J. S., Elyaman, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4203 · Cited by 302 · see citing works
Self-citationLorenzo, T. P., Peakman, M., & Roep, B. O. (2007) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03244.x · Cited by 261 · see citing works
A diabetes-susceptible HLA haplotype is best defined by a combination of HLA-DR and -DQ alleles.
Sheehy, M. J., Scharf, S., Rowe, J. R., et al. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113965 · Cited by 258 · see citing works
No Alterations in the Frequency of FOXP3+ Regulatory T-Cells in Type 1 Diabetes
Brusko, T. M., Wasserfall, C. H., MCGRAIL, K. M., Schatz, R., Viener, H. L., Schatz, D., Haller, M. J., Rockell, J., Gottlieb, P. A., Clare-Salzler, M. J., et al. (2007) · Diabetes · doi:10.2337/db06-1248 · Cited by 253 · see citing works
Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells
Ooi, J. D., Petersen, J., Tan, Y. H., Huynh, M., Willett, Z. J., Ramarathinam, S. H., Eggenhuizen, P. J., Loh, K. L., Watson, K. A., Gan, P. Y., et al. (2017) · Nature · doi:10.1038/nature22329 · Cited by 218 · see citing works
Redondo, M. J., Steck, A. K., & Pugliese, A. (2018) · Pediatric Diabetes · doi:10.1111/pedi.12597 · Cited by 216 · see citing works
Insulin as an autoantigen in NOD/human diabetes.
Zhang, L., Nakayama, M., & Eisenbarth, G. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.11.005 · Cited by 215 · see citing works
Antigen Targets of Type 1 Diabetes AutoimmunityPreprint
Roep, B. O., & Peakman, M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007781 · Cited by 212 · see citing works
CD4+CD25high regulatory T cells in human autoimmune diabetes
Putnam, A. L., Vendrame, F., Dotta, F., & Gottlieb, P. A. (2005) · Journal of Autoimmunity · doi:10.1016/j.jaut.2004.11.004 · Cited by 206 · see citing works
A Mechanism for the Major Histocompatibility Complex–linked Resistance to Autoimmunity
Schmidt, D., Verdaguer, J., Averill, N., & Santamaría, P. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.7.1059 · Cited by 195 · see citing works
Maggi, E., Cosmi, L., Liotta, F., Romagnani, P., Romagnani, S., & Annunziato, F. (2005) · Autoimmunity Reviews · doi:10.1016/j.autrev.2005.04.010 · Cited by 183 · see citing works
Pathiraja, V., Kuehlich, J. P., Campbell, P. D., Krishnamurthy, B., Loudovaris, T., Coates, P. T., Brodnicki, T. C., O’Connell, P. J., Kedzierska, K., Rodda, C. P., et al. (2014) · Diabetes · doi:10.2337/db14-0858 · Cited by 164 · see citing works
MHC Class II Polymorphisms, Autoreactive T-Cells, and Autoimmunity
Tsai, S. J., & Santamaría, P. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00321 · Cited by 162 · see citing works
Hermann, R., Turpeinen, H., Laine, A.-P., Veijola, R., Knip, M., Simell, O., Sipilä, I., Åkerblom, H. K., & Ilonen, J. (2003) · Tissue Antigens · doi:10.1034/j.1399-0039.2003.00071.x · Cited by 146 · see citing works
The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update
the TEDDY Study Group, Rewers, M., Hyöty, H., Lernmark, Å., Hagopian, W., She, J., Schatz, D., Ziegler, A., Toppari, J., Akolkar, B., et al. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1113-2 · Cited by 136 · see citing works
Novak, E. J., Liu, A. W., Gebe, J. A., Falk, B. A., Nepom, G. T., Koelle, D. M., & Kwok, W. W. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.11.6665 · Cited by 135 · see citing works
Self-citationDaniel, C., Weigmann, B., Bronson, R. T., & von Boehmer, H. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110574 · Cited by 133 · see citing works
Hyöty, H. (2016) · Pediatric Diabetes · doi:10.1111/pedi.12370 · Cited by 127 · see citing works
Yang, J., Chow, I., Sosinowski, T., Torres-Chinn, N., Greenbaum, C. J., James, E. A., Kappler, J. W., Davidson, H. W., & Kwok, W. W. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416864111 · Cited by 124 · see citing works
Self-citationCoexpression of TIGIT and FCRL3 Identifies Helios+ Human Memory Regulatory T Cells
Bin Dhuban, K., d’Hennezel, E., Nashi, E., Bar-Or, A., Rieder, S., Shevach, E. M., Nagata, S., & Piccirillo, C. A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1401803 · Cited by 117 · see citing works
HLA-DQB1 codon 57 is critical for peptide binding and recognition.
Kwok, W. W., Domeier, M. E., Johnson, M., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.1253 · Cited by 110 · see citing works
Self-citationYang, J., Danke, N. A., Berger, D., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.5.2781 · Cited by 109 · see citing works
Self-citationT‐cell receptor affinity in thymic development
Moran, A. E., & Hogquist, K. A. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03547.x · Cited by 103 · see citing works
Modulation of Type 1 Diabetes Risk by the Intestinal Microbiome
Knip, M., & Honkanen, J. K. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0933-9 · Cited by 99 · see citing works
Silverman, M. A., Kua, L. H., Tanca, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1712280114 · Cited by 88 · see citing works
Erlich, H. A., Griffith, R. L., Bugawan, T. L., Ziegler, R., Alper, C. A., & Eisenbarth, G. S. (1991) · Diabetes · doi:10.2337/diab.40.4.478 · Cited by 83 · see citing works
Nowak, A., Lock, D., Bächer, P., Hohnstein, T., Vogt, K., Gottfreund, J., Giehr, P., Polansky, J. K., Sawitzki, B., Kaiser, A., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00199 · Cited by 78 · see citing works
Ettinger, R. A., & Kwok, W. W. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.5.2365 · Cited by 77 · see citing works
Self-citationRobertson, C. C., & Rich, S. S. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.01.006 · Cited by 72 · see citing works
Uchtenhagen, H., Rims, C. R., Blahnik, G., Chow, I., Kwok, W. W., Buckner, J. H., & James, E. A. (2016) · Nature Communications · doi:10.1038/ncomms12614 · Cited by 71 · see citing works
Self-citationNovel antigens in type 1 diabetes: The importance of ZnT8
Wenzlau, J. M., Frisch, L. M., Gardner, T. J., Sarkar, S. A., Hutton, J. C., & Davidson, H. W. (2009) · Current Diabetes Reports · doi:10.1007/s11892-009-0019-4 · Cited by 62 · see citing works
Elkord, E. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00276 · Cited by 61 · see citing works
Yang, J. H. M., Cutler, A. J., Ferreira, R. C., Reading, J. L., Cooper, N. J., Wallace, C., Pamela, C., Smyth, D. J., Boyce, C. S., Gao, G., et al. (2015) · Diabetes · doi:10.2337/db15-0516 · Cited by 59 · see citing works
Self-citationPrimary Association of HLA-DQw8 With Type I Diabetes in DR4 Patients
Owerbach, D., Gunn, S., & Gabbay, K. H. (1989) · Diabetes · doi:10.2337/diab.38.7.942 · Cited by 55 · see citing works
Insulin as a Primary Autoantigen for Type 1A Diabetes
Jasinski, J., & Eisenbarth, G. S. (2005) · Journal of Immunology Research · doi:10.1080/17402520500078204 · Cited by 51 · see citing works
Eerligh, P., van Lummel, M., Zaldumbide, A., Moustakas, A. K., Duinkerken, G., Bondinas, G. P., Koeleman, B. P. C., Papadopoulos, G. K., & Roep, B. O. (2011) · Genes and Immunity · doi:10.1038/gene.2011.24 · Cited by 49 · see citing works
Yoshida, K., Corper, A. L., Herro, R., Jabrì, B., Wilson, I. A., & Teyton, L. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41502 · Cited by 48 · see citing works
Tait, B. D., Drummond, B. P., Varney, M. D., et al. (1995) · International Journal of Immunogenetics · doi:10.1111/j.1744-313x.1995.tb00245.x · Cited by 47 · see citing works
Yang, J., James, E. A., Sanda, S., Greenbaum, C. J., & Kwok, W. W. (2012) · Immunology · doi:10.1111/imm.12034 · Cited by 44 · see citing works
Self-citationChow, I.-T., Yang, J., Gates, T., James, E., Mai, D., Greenbaum, C., & Kwok, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112882 · Cited by 38 · see citing works
Self-citationBeneficial autoimmunity in Type 1 diabetes mellitus
Hauben, E., Roncarolo, M., Nevo, U., & SCHWARTZ, M. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.03.004 · Cited by 30 · see citing works
Öberg, M., Bohn, T., & Larsson, U. (2014) · Journal of the American Academy of Audiology · doi:10.3766/jaaa.25.9.7 · Cited by 29 · see citing works
Hänninen, A. L. M., Soilu‐Hänninen, M., Hampe, C. S., et al. (2010) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1083 · Cited by 28 · see citing works
Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures
Kuhn, C., Besançon, A., Lemoine, S., You, S., Marquet, C., Candon, S., & Chatenoud, L. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2016.05.002 · Cited by 28 · see citing works
Yang, J., Wen, X., Xu, H., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601570 · Cited by 27 · see citing works
Self-citationEpitope Stealing as a Mechanism of Dominant Protection by HLA-DQ6 in Type 1 Diabetes
van Lummel, M., Buis, D. T. P., Ringeling, C., et al. (2019) · Diabetes · doi:10.2337/db18-0501 · Cited by 26 · see citing works
A novel and rapid method to quantify Treg mediated suppression of CD4 T cells
Long, A. E., Tatum, M., Mikacenic, C. R., & Buckner, J. H. (2017) · Journal of Immunological Methods · doi:10.1016/j.jim.2017.06.009 · Cited by 19 · see citing works
Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex
Bettini, M. L., & Bettini, M. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00351 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Saggau, C., Bacher, P., Esser, D., Rasa, M., Meise, S., Mohr, N., Kohlstedt, N., Hutloff, A., Schacht, S.-S., Dargvainiene, J., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.08.005 · Cited by 79 · see citing works
- Authors
- Wen, X., Yang, J., James, E., Chow, I.-T., Reijonen, H., & Kwok, W. W.
- Affiliations
- Benaroya Research Institute (US)
- City Of Hope National Medical Center (US)
- University of Washington (US)
- Corresponding author
- Kwok, William W.
- Venue
- Science Immunology
- Published
- 2020-02-14
- Volume
- 5
- Issue
- 44
- ISSN
- 2470-9468 (ISSN-L)
- PMC
- PMC7566980
- OpenAlex
- W3006056392
- Cited by
- 35
- References
- 67
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 4
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH Office of the Director (DP3 DK097653, DP3 DK106909)
- Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D036)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- type 1 diabetes, islet antigens, regulatory T cells, CD4+ T cells, effector T cells, IL-10, disease protection, HLA-DQ6
- MeSH terms
- Diabetes Mellitus, Type 1, Haplotypes, Humans, CD4-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Insulin-Secreting Cells, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review