HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lejon C., K. Articles by Fathman, G. Search for Related Content PubMed PubMed Citation Articles by Lejon C., K. Articles by Fathman, G.

Isolation of Self Antigen-Reactive Cells from Inflamed Islets of Nonobese Diabetic Mice Using CD4^high Expression as a Marker¹

Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305

The low precursor frequency of Ag-reactive CD4⁺ T cells has been a barrier to the study of CD4⁺ T cell responses to conventional Ags as well as CD4⁺ T cell responses to autoantigens recognized during the course of an autoimmune disease. We have recently reported that all "conventional Ag" reactive CD4⁺ T cells are contained within the subpopulation expressing high levels of the CD4 molecule, termed CD4^high. We have identified a CD4^high population in the islets of Langerhans of prediabetic nonobese diabetic (NOD) mice that is extremely potent in transferring disease. As few as 500 CD4^high islet-infiltrating CD4⁺ T cells transferred insulin-dependent diabetes mellitus to CD8 reconstituted NOD-SCID mice within 30 days of transfer. In contrast, CD4^high T cells isolated from either NOD spleen or salivary glands did not transfer insulin-dependent diabetes mellitus into similar CD8-reconstituted NOD-SCID recipients. These data indicate that the precursor frequency of NOD islet-reactive, pathogenic CD4⁺ T cells is much higher in the prediabetic NOD pancreas than in these other organs. The islet-infiltrating CD4^high T cells displayed selected memory markers, by cell surface analysis, and displayed a Th 1 phenotype by RNase protection assay, but had a marked decrease in IL-4 mRNA determined by quantitative real time PCR when compared with the less pathogenic CD4^normal islet-infiltrating T cells. Use of the CD4^high marker to select Ag activated T cells represents a tool to isolate and study pathogenic CD4⁺ T cells from autoimmune lesions in which the Ag has not been previously defined.

This article has been cited by other articles:

				N. E. Standifer, S. Stacy, E. Kraig, and A. J. Infante Discrete T Cell Populations with Specificity for a Neo-Self-Antigen Bear Distinct Imprints of Tolerance J. Immunol., March 15, 2007; 178(6): 3544 - 3550. [Abstract] [Full Text] [PDF]

				A. Quinn, M. McInerney, D. Huffman, B. McInerney, S. Mayo, K. Haskins, and E. Sercarz T cells to a dominant epitope of GAD65 express a public CDR3 motif Int. Immunol., June 1, 2006; 18(6): 967 - 979. [Abstract] [Full Text] [PDF]

				N. Seddiki, B. Santner-Nanan, S. G. Tangye, S. I. Alexander, M. Solomon, S. Lee, R. Nanan, and B. F. de Saint Groth Persistence of naive CD45RA+ regulatory T cells in adult life Blood, April 1, 2006; 107(7): 2830 - 2838. [Abstract] [Full Text] [PDF]

				C.-H. Lee, Y.-G. Chen, J. Chen, P. C. Reifsnyder, D. V. Serreze, M. Clare-Salzler, M. Rodriguez, C. Wasserfall, M. A. Atkinson, and E. H. Leiter Novel Leptin Receptor Mutation in NOD/LtJ Mice Suppresses Type 1 Diabetes Progression: II. Immunologic Analysis Diabetes, January 1, 2006; 55(1): 171 - 178. [Abstract] [Full Text] [PDF]

				H.-Y. Qin, P. Chaturvedi, and B. Singh In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-{gamma}/TNF-{alpha} Int. Immunol., December 1, 2004; 16(12): 1723 - 1732. [Abstract] [Full Text] [PDF]

				R. A. O'Connor and E. Devaney Nitric Oxide Limits the Expansion of Antigen-Specific T Cells in Mice Infected with the Microfilariae of Brugia pahangi Infect. Immun., November 1, 2002; 70(11): 5997 - 6004. [Abstract] [Full Text] [PDF]

				V. Szanya, J. Ermann, C. Taylor, C. Holness, and C. G. Fathman The Subpopulation of CD4+CD25+ Splenocytes That Delays Adoptive Transfer of Diabetes Expresses L-Selectin and High Levels of CCR7 J. Immunol., September 1, 2002; 169(5): 2461 - 2465. [Abstract] [Full Text] [PDF]

				H. Reijonen, E. J. Novak, S. Kochik, A. Heninger, A. W. Liu, W. W. Kwok, and G. T. Nepom Detection of GAD65-Specific T-Cells by Major Histocompatibility Complex Class II Tetramers in Type 1 Diabetic Patients and At-Risk Subjects Diabetes, May 1, 2002; 51(5): 1375 - 1382. [Abstract] [Full Text] [PDF]

				D. H. Wagner Jr., G. Vaitaitis, R. Sanderson, M. Poulin, C. Dobbs, and K. Haskins Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes PNAS, March 19, 2002; 99(6): 3782 - 3787. [Abstract] [Full Text] [PDF]

				E. J. Novak, S. A. Masewicz, A. W. Liu, A. Lernmark, W. W. Kwok, and G. T. Nepom Activated human epitope-specific T cells identified by class II tetramers reside within a CD4high, proliferating subset Int. Immunol., June 1, 2001; 13(6): 799 - 806. [Abstract] [Full Text] [PDF]

				M. Fasso, N. Anandasabapathy, F. Crawford, J. Kappler, C. G. Fathman, and W. M. Ridgway T Cell Receptor (TCR)-mediated Repertoire Selection and Loss of TCR V{beta} Diversity during the Initiation of a CD4+ T Cell Response In Vivo J. Exp. Med., December 11, 2000; 192(12): 1719 - 1730. [Abstract] [Full Text] [PDF]