NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells.
The phenotype of NFATc2(-/-) c3(-/-) (double knockout [DKO]) mice implies a disturbed regulation of T cell responses, evidenced by massive lymphadenopathy, splenomegaly, and autoaggressive phenomena. The population of CD4(+) CD25(+) T cells from DKO mice lacks regulatory capacity, except a small subpopulation that highly expresses glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) and CD25. However, neither wild-type nor DKO CD4(+) CD25(+) regulatory T cells (T reg cells) are able to suppress proliferation of DKO CD4(+) CD25(-) T helper cells. Therefore, combined NFATc2/c3 deficiency is compatible with the development of CD4(+) CD25(+) T reg cells but renders conventional CD4(+) T cells unresponsive to suppression, underlining the importance of NFAT proteins for sustaining T cell homeostasis.
Bopp
Tobias
T
Institute of Immunology, Johannes Gutenberg University, 55131 Mainz, Germany.
Palmetshofer
Alois
A
Serfling
Edgar
E
Heib
Valeska
V
Schmitt
Steffen
S
Richter
Christoph
C
Klein
Matthias
M
Schild
Hansjörg
H
Schmitt
Edgar
E
Stassen
Michael
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D053450:Glucocorticoid-Induced TNFR-Related Protein; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; C494009:Nfatc3 protein, mouse; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; D014157:Transcription Factors