Transgenic Bcl-3 slows T cell proliferation.
Immunological adjuvants, such as bacterial LPS, increase the mRNA levels of the IkB-related NF-kappaB 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.
Bassetti
Michael F J
MF
Integrated Department of Immunology, University of Colorado Denver Health Sciences Center, Denver, CO 80206, USA.
White
Janice
J
Kappler
John W
JW
Marrack
Philippa
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D000276:Adjuvants, Immunologic; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors