Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 31, 2013, Pages

  Sinclair, Charles ^a   Bains, Iren ^a   Yates, Andrew J ^b,c   Seddon, Benedict ^a  

^a NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

^b Department of Systems and Computational Biology ^*  (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

CD4 T cells; CD8 T cells

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; HLA ANTIGEN CLASS 1;

ADAPTIVE IMMUNITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CD4 CD8 RATIO; CELL DIFFERENTIATION; CELL LINEAGE; CELL MATURATION; CELL SELECTION; CELL STRESS; CELL SYNCHRONIZATION; CONTROLLED STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; SUSCEPTIBLE POPULATION; THYMOCYTE; ANIMAL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEATH; CELLULAR IMMUNITY; CYTOLOGY; IMMUNOLOGY; KNOCKOUT MOUSE;

ANIMALS; CD4-CD8 RATIO; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL DEATH; HISTOCOMPATIBILITY ANTIGENS CLASS I; IMMUNITY, CELLULAR; MICE; MICE, KNOCKOUT; THYMOCYTES;

EID: 84881096188     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1304859110     Document Type: Article

References (46)

1. Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1979) Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci USA 76(8): 4061-4065.
2. Bouillet P, et al. (2002) BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415(6874):922-926.
3. Hernández-Hoyos G, Anderson MK, Wang C, Rothenberg EV, Alberola-Ila J (2003) GATA-3 expression is controlled by TCR signals and regulates CD4/CD8 differentiation. Immunity 19(1):83-94.
4. Wang L, et al. (2008) Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells. Nat Immunol 9(10): 1122-1130.
5. Sato T, et al. (2005) Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes. Immunity 22(3):317-328.
6. Park JH, et al. (2010) Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat Immunol 11(3):257-264.
7. Woolf E, et al. (2003) Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proc Natl Acad Sci USA 100(13):7731-7736.
8. Egawa T, Tillman RE, Naoe Y, Taniuchi I, Littman DR (2007) The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med 204(8):1945-1957.
9. Saini M, et al. (2010) Regulation of Zap70 expression during thymocyte development enables temporal separation of CD4 and CD8 repertoire selection at different signaling thresholds. Sci Signal 3(114):ra23.
10. Egerton M, Scollay R, Shortman K (1990) Kinetics of mature T-cell development in the thymus. Proc Natl Acad Sci USA 87(7):2579-2582.
11. Yagi H, et al. (2000) Immunosuppressant FTY720 inhibits thymocyte emigration. Eur J Immunol 30(5):1435-1444.
12. de Boer J, et al. (2003) Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur J Immunol 33(2):314-325.
13. Williams O, Norton T, Halligey M, Kioussis D, Brady HJ (1998) The action of Bax and bcl-2 on T cell selection. J Exp Med 188(6):1125-1133.
14. Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR (2010) The BCL-2 family reunion. Mol Cell 37(3):299-310.
15. Chao DT, et al. (1995) Bcl-XL and Bcl-2 repress a common pathway of cell death. J Exp Med 182(3):821-828.
16. Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ (1991) bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67(5):879-888.
17. Strasser A, Harris AW, Cory S (1991) bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67(5):889-899.
18. Hu Q, Sader A, Parkman JC, Baldwin TA (2009) Bim-mediated apoptosis is not necessary for thymic negative selection to ubiquitous self-antigens. J Immunol 183(12):7761-7767.
19. Pellegrini M, et al. (2004) Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J Exp Med 200(9):1189-1195.
20. Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4(4):350-354.
21. Gray DH, et al. (2012) The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of organ-specific antigens. Immunity 37(3):451-462.
22. Yamashita I, Nagata T, Tada T, Nakayama T (1993) CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection. Int Immunol 5(9):1139-1150.
23. Merkenschlager M, et al. (1997) How many thymocytes audition for selection? J Exp Med 186(7):1149-1158.
24. Merkenschlager M, Benoist C, Mathis D (1994) Evidence for a single-niche model of positive selection. Proc Natl Acad Sci USA 91(24):11694-11698.
25. Van Laethem F, Tikhonova AN, Singer A (2012) MHC restriction is imposed on a diverse T cell receptor repertoire by CD4 and CD8 co-receptors during thymic selection. Trends Immunol 33(9):437-441.
26. Garcia KC (2012) Reconciling views on T cell receptor germline bias for MHC. Trends Immunol 33(9):429-436.
27. Stritesky GL, et al. (2013) Murine thymic selection quantified using a unique method to capture deleted T cells. Proc Natl Acad Sci USA 110(12):4679-4684.
28. Bouillet P, et al. (1999) Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286(5445): 1735-1738.
29. Polic B, Kunkel D, Scheffold A, Rajewsky K (2001) How alpha beta T cells deal with induced TCR alpha ablation. Proc Natl Acad Sci USA 98(15):8744-8749.
30. Seddon B, Zamoyska R (2002) TCR signals mediated by Src family kinases are essential for the survival of naive T cells. J Immunol 169(6):2997-3005.
31. den Braber I, et al. (2012) Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 36(2):288-297.
32. Koller BH, Marrack P, Kappler JW, Smithies O (1990) Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science 248(4960): 1227-1230.
33. Madsen L, et al. (1999) Mice lacking all conventional MHC class II genes. Proc Natl Acad Sci USA 96(18):10338-10343.
34. Mombaerts P, et al. (1992) RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68(5):869-877.
35. Mamalaki C, et al. (1993) Positive and negative selection in transgenic mice expressing a T-cell receptor specific for influenza nucleoprotein and endogenous superantigen. Dev Immunol 3(3):159-174.
36. Hogquist KA, et al. (1994) T cell receptor antagonist peptides induce positive selection. Cell 76(1):17-27.
37. Negishi I, et al. (1995) Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376(6539):435-438.
38. Brady HJ, Gil-Gómez G, Kirberg J, Berns AJ (1996) Bax alpha perturbs T cell development and affects cell cycle entry of T cells. EMBO J 15(24):6991-7001.
39. Sinclair C, Saini M, Schim van der Loeff I, Sakaguchi S, Seddon B (2011) The long-term survival potential of mature T lymphocytes is programmed during development in the thymus. Sci Signal 4(199):ra77.
40. de la Cueva T, Naranjo A, de la Cueva E, Rubio D (2007) Refinement of intrathymic injection in mice. Lab Anim (NY) 36(5):27-32.
41. Christodoulou DC, Gorham JM, Herman DS, Seidman JG (2011) Construction of normalized RNA-seq libraries for next-generation sequencing using the crab duplexspecific nuclease. Curr Protoc Mol Biol, Chapter 4:Unit4.12.
42. Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol 11(10):R106.
43. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5(7):621-628.
44. Thomas-Vaslin V, Altes HK, de Boer RJ, Klatzmann D (2008) Comprehensive assessment and mathematical modeling of T cell population dynamics and homeostasis. J Immunol 180(4):2240-2250.
45. McCaughtry TM, Wilken MS, Hogquist KA (2007) Thymic emigration revisited. J Exp Med 204(11):2513-2520.
46. Rooke R, Waltzinger C, Benoist C, Mathis D (1997) Targeted complementation of MHC class II deficiency by intrathymic delivery of recombinant adenoviruses. Immunity 7(1):123-134.