Phospho-flow cytometry based analysis of differences in T cell receptor signaling between regulatory T cells and CD4+ T cells

Journal of Immunological Methods

Volumn 376, Issue 1-2, 2012, Pages 1-12

  Hanschen, Marc ^a,b   Tajima, Goro ^a   O'Leary, Fionnuala ^a   Hoang, Kimberly ^a   Ikeda, Kimiko ^a   Lederer, James A ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

CD4+ T regulatory cells; Differential cell activation; Intracellular signaling; T cell activation; T cell receptor

Indexed keywords

BACTERIAL ANTIGEN; PROTEIN KINASE C; PROTEIN KINASE ZAP 70; SUPERANTIGEN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ANIMAL CELL; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; FLOW CYTOMETRY; IMMUNOSTIMULATION; IN VITRO STUDY; IN VIVO STUDY; KINETICS; LYMPH NODE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; ENTEROTOXINS; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; ISOENZYMES; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PROTEIN KINASE C; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; STATISTICS, NONPARAMETRIC; T-LYMPHOCYTES, REGULATORY; ZAP-70 PROTEIN-TYROSINE KINASE;

BACTERIA (MICROORGANISMS); MUS;

EID: 84856554897     PISSN: 00221759     EISSN: 18727905     Source Type: Journal    
DOI: 10.1016/j.jim.2011.08.023     Document Type: Article

References (34)

1. Au-Yeung B.B., Deindl S., Hsu L.Y., Palacios E.H., Levin S.E., Kuriyan J., Weiss A. The structure, regulation, and function of ZAP-70. Immunol. Rev. 2009, 228:41.
2. Bacon K.B., Premack B.A., Gardner P., Schall T.J. Activation of dual T cell signaling pathways by the chemokine RANTES. Science 1995, 269:1727.
3. Baier G., Telford D., Giampa L., Coggeshall K.M., Baier-Bitterlich G., Isakov N., Altman A. Molecular cloning and characterization of PKC theta, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. J. Biol. Chem. 1993, 268:4997.
4. Barnden M.J., Allison J., Heath W.R., Carbone F.R. Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements. Immunol. Cell Biol. 1998, 76:34.
5. Bi K., Tanaka Y., Coudronniere N., Sugie K., Hong S., van Stipdonk M.J., Altman A. Antigen-induced translocation of PKC-theta to membrane rafts is required for T cell activation. Nat. Immunol. 2001, 2:556.
6. Chan A.C., Dalton M., Johnson R., Kong G.H., Wang T., Thoma R., Kurosaki T. Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function. EMBO J. 1995, 14:2499.
7. Chow S., Patel H., Hedley D.W. Measurement of MAP kinase activation by flow cytometry using phospho-specific antibodies to MEK and ERK: potential for pharmacodynamic monitoring of signal transduction inhibitors. Cytometry 2001, 46:72.
8. Coudronniere N., Villalba M., Englund N., Altman A. NF-kappa B activation induced by T cell receptor/CD28 costimulation is mediated by protein kinase C-theta. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:3394.
9. Crellin N.K., Garcia R.V., Levings M.K. Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells. Blood 2007, 109:2014.
10. Crellin N.K., Garcia R.V., Levings M.K. Flow cytometry-based methods for studying signaling in human CD4+CD25+FOXP3+ T regulatory cells. J. Immunol. Methods 2007, 324:92.
11. Delves P.J., Roitt I.M. The immune system. Second of two parts. N. Engl. J. Med. 2000, 343:108.
12. Farber D.L. Biochemical signaling pathways for memory T cell recall. Semin. Immunol. 2009, 21:84.
13. Frauwirth K.A., Thompson C.B. Activation and inhibition of lymphocytes by costimulation. J. Clin. Invest. 2002, 109:295.
14. Gavin M.A., Torgerson T.R., Houston E., DeRoos P., Ho W.Y., Stray-Pedersen A., Ocheltree E.L., Greenberg P.D., Ochs H.D., Rudensky A.Y. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:6659.
15. Grakoui A., Bromley S.K., Sumen C., Davis M.M., Shaw A.S., Allen P.M., Dustin M.L. The immunological synapse: a molecular machine controlling T cell activation. Science 1999, 285:221.
16. Hayashi K., Altman A. Protein kinase C theta (PKCtheta): a key player in T cell life and death. Pharmacol. Res. 2007, 55:537.
17. Hickman S.P., Yang J., Thomas R.M., Wells A.D., Turka L.A. Defective activation of protein kinase C and Ras-ERK pathways limits IL-2 production and proliferation by CD4+CD25+ regulatory T cells. J. Immunol. 2006, 177:2186.
18. Isakov N., Altman A. Protein kinase C(theta) in T cell activation. Annu. Rev. Immunol. 2002, 20(761-94):761.
19. Josefowicz S.Z., Rudensky A. Control of regulatory T cell lineage commitment and maintenance. Immunity 2009, 30:616.
20. Krutzik P.O., Nolan G.P. Intracellular phospho-protein staining techniques for flow cytometry: monitoring single cell signaling events. Cytometry A 2003, 55:61.
21. Li L., Godfrey W.R., Porter S.B., Ge Y., June C.H., Blazar B.R., Boussiotis V.A. CD4+CD25+ regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy. Blood 2005, 106:3068.
22. Lucas P.C., lister-Lucas L.M., Nunez G. NF-kappaB signaling in lymphocytes: a new cast of characters. J. Cell Sci. 2004, 117:31.
23. Matarese G., De R.V., La C.A. Regulatory CD4 T cells: sensing the environment. Trends Immunol. 2008, 29:12.
24. Meller N., Elitzur Y., Isakov N. Protein kinase C-theta (PKCtheta) distribution analysis in hematopoietic cells: proliferating T cells exhibit high proportions of PKCtheta in the particulate fraction. Cell. Immunol. 1999, 193:185.
25. Monks C.R., Kupfer H., Tamir I., Barlow A., Kupfer A. Selective modulation of protein kinase C-theta during T-cell activation. Nature 1997, 385:83.
26. Monks C.R., Freiberg B.A., Kupfer H., Sciaky N., Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998, 395:82.
27. Mustelin T., Tasken K. Positive and negative regulation of T-cell activation through kinases and phosphatases. Biochem. J. 2003, 371:15.
28. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155:1151.
29. Thebault S., Ochoa-Garay J. Characterization of TCR-induced phosphorylation of PKCtheta in primary murine lymphocytes. Mol. Immunol. 2004, 40:931.
30. Tsang J.Y., Camara N.O., Eren E., Schneider H., Rudd C., Lombardi G., Lechler R. Altered proximal T cell receptor (TCR) signaling in human CD4+CD25+ regulatory T cells. J. Leukoc. Biol. 2006, 80:145.
31. Wan Y.Y., Flavell R.A. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007, 445:766.
32. Wang J., Ioan-Facsinay A., van d.V, Huizinga T.W., Toes R.E. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 2007, 37:129.
33. Watson A.R., Lee W.T. Defective T cell receptor-mediated signal transduction in memory CD4 T lymphocytes exposed to superantigen or anti-T cell receptor antibodies. Cell. Immunol. 2006, 242:80.
34. Williams B.L., Irvin B.J., Sutor S.L., Chini C.C., Yacyshyn E., Bubeck W.J., Dalton M., Chan A.C., Abraham R.T. Phosphorylation of Tyr319 in ZAP-70 is required for T-cell antigen receptor-dependent phospholipase C-gamma1 and Ras activation. EMBO J. 1999, 18:1832.