Altered T-dependent antigen responses and development of autoimmune symptoms in mice lacking E2A in T lymphocytes.
E2A has been shown to be an important transcription factor downstream of the T-cell receptor (TCR) signal during T-cell development. The TCR signal is known to elicit different cellular responses at different stages of T-cell development. Whether E2A is still required for normal TCR signalling in mature T cells is unknown. Here we examined T-cell function after disruption of the E2A gene exclusively in the T-cell lineage. The conditional E2A-deficient mice show enhanced humoral immunity to a T-dependent antigen. We further show that E2A is involved in regulating TCR-induced T-cell proliferation events. However, E2A seems to play opposite roles in naïve and effector T cells. In the absence of E2A, TCR-induced proliferation is increased in naïve T cells and decreased in effector T cells. At older ages, these mice frequently develop antinuclear antibodies and proteinuria. Our studies suggest that E2A regulates T-cell function and the loss of E2A may promote age-dependent autoimmune diseases.
Pan
Lihua
L
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Bradney
Curtis
C
Zheng
Biao
B
Zhuang
Yuan
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D007114:Immunization; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011507:Proteinuria / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000974:Antibodies, Antinuclear; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; C407909:TCF3 protein, human