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Transgenic Bcl-3 slows T cell proliferation

By Michael F. J. Bassetti, Janice White, John W. Kappler and Philippa Marrack

Abstract

Immunological adjuvants, such as bacterial LPS, increase the mRNA levels of the IkB-related NF-κB transcriptional transactivator, Bcl-3, in activated T cells. Adjuvants also increase the life expectancy of activated T cells, as does over-expression of Bcl-3, suggesting that Bcl-3 is part of the pathway whereby adjuvants affect T cell lifespans. However, previous reports, confirmed here, show that adjuvants also increase the life expectancies of Bcl-3-deficient T cells, making Bcl-3’s role and effects in adjuvant-induced survival uncertain. To investigate the functions of Bcl-3 further, here we confirm the adjuvant-induced expression of Bcl-3 mRNA and show Bcl-3 induction at the protein level. Bcl-3 was expressed in mice via a transgene driven by the human CD2 promoter. Like other protective events, over-expression of Bcl-3 slows T cell activation very early in T cell responses to antigen, both in vitro and in vivo. This property was intrinsic to the T cells over-expressing the Bcl-3 and did not require Bcl-3 expression by other cells such as antigen-presenting cells

Topics: Original Research Papers
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:2660861
Provided by: PubMed Central

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Citations

  1. (2006). A pathway for tumor necrosis factor-alpha-induced Bcl10 nuclear translocation. Bcl10 is up-regulated by NF-kappaB and phosphorylated by Akt1 and then complexes with Bcl3 to enter the nucleus.
  2. (1998). A role for FADD in Tcell activation and development. Immunity 8:439.
  3. A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance.
  4. A short domain within Bcl-3 is responsible for its lymphocyte survival activity.
  5. and NFkappaB p50-p50 homodimers act as transcriptional repressors in tolerant CD4+ T cells.
  6. (2004). Caspase inhibition blocks human T cell proliferation by suppressing appropriate regulation of IL-2, CD25, and cell cycle-associated proteins.
  7. (1995). CD28 costimulation can promote Tcell survival by enhancing the expression of Bcl-XL.
  8. (1999). CD4+ T cell division in irradiated mice requires peptides distinct from those responsible for thymic selection.
  9. (2006). CD8 Tcells require Bcl-3 for maximal gamma interferon production upon secondary exposure to antigen.
  10. (2005). Cellular FLICEinhibitory protein is required for Tcell survival and cycling.
  11. (1997). Critical roles for the Bcl-3 oncoprotein in Tcell-mediated immunity, splenic microarchitecture, and germinal center reactions. Immunity 6:479.
  12. (1996). Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation.
  13. (2004). Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor.
  14. (2005). Cutting edge: Bcl-3 up-regulation by signal 3 cytokine (IL-12) prolongs survival of antigen-activated CD8 T cells.
  15. (1989). Cytogenetic and molecular changes in chronic B-cell leukemia.
  16. (1998). Cytokine-induced survival of activated T cells in vitro and in vivo.
  17. Defining the antigen-specific T-cell response to vaccination Bcl-3 inhibits T cell activation and death 347and poly(I:C)/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity.
  18. (1997). Diverse effects of BCL3 phosphorylation on its modulation of NF-kappaB p52 homodimer binding to DNA.
  19. (1961). Effectiveness of lipid and lipidophilic substances as adjuvants.
  20. (2008). FADD and the NF-kappaB family member Bcl-3 regulate complementary pathways to control T-cell survival and proliferation.
  21. (2006). IL-12-programmed long-term CD8+ T cell responses require STAT4.
  22. (2001). Immunological adjuvants promote activated T cell survival via induction of Bcl-3.
  23. (2002). Immunology of vaccination.
  24. (1995). Improved version of a human CD2 minigene based vector for T cell-specific expression in transgenic mice.
  25. (1997). Inflammatory cytokines enhance the in vivo clonal expansion and differentiation of antigen-activated CD4+ T cells.
  26. (1997). Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4.
  27. (1996). Interleukin-2 receptor common gamma-chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: selective induction of anti-apoptotic (bcl-2, bcl-xL) but not pro-apoptotic (bax, bcl-xS) gene expression.
  28. (1995). Lipopolysaccharide interferes with the induction of peripheral T cell death.
  29. (1991). Mouse bcl-3: cDNA structure, mapping and stage-dependent expression in B lymphocytes. Oncogene
  30. (2001). NFkappa B-inducible BCL-3 expression is an autoregulatory loop controlling nuclear p50/NF-kappa B1 residence.
  31. (2004). Protein phosphorylation as a key mechanism for the regulation of BCL-3 activity.
  32. (1989). Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Res.
  33. (2007). Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD.
  34. (2005). Regulation of Bcl-3 through interaction with the Lck tyrosine kinase.
  35. (1996). Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.
  36. (1988). Selftolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex.
  37. (2006). Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury by ensuring the integrity of cytotoxic granules.
  38. (1998). Signaldependent translation of a regulatory protein, Bcl-3, in activated human platelets.
  39. (2002). Stronger correlation of bcl-3 than bcl-2, bcl-xL, costimulation, or antioxidants with adjuvant-induced Tcell survival.
  40. (1999). Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II and cytokine milieu.
  41. (2002). T cell memory.
  42. (1973). Termination of tolerance to human gamma globulin in mice by antigen and bacterial lipopolysaccharide (endotoxin).
  43. (1997). The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry.
  44. (1999). The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators.
  45. (1993). The bcl-3 protooncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner.
  46. (1990). The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control.
  47. The candidate proto-oncogene bcl-3encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers. Genes Dev.
  48. (1993). The oncoprotein Bcl-3 can facilitate NF-kappa B-mediated transactivation by removing inhibiting p50 homodimers from select kappa B sites.
  49. (1993). The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers.
  50. (2007). The proapoptotic factors Bax and Bak regulate Tcell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis.
  51. (1972). The role of Tcells and adjuvant in the immune response of mice to foreign erythrocytes.
  52. (1995). Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation.
  53. (2004). Toll-like receptor ligands directly promote activated CD4+ Tcell survival.

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