STIM1-independent T cell development and effector function in vivo.
Store-operated Ca(2+) entry (SOCE) is believed to be of pivotal importance in T cell physiology. To test this hypothesis, we generated mice constitutively lacking the SOCE-regulating Ca(2+) sensor stromal interaction molecule 1 (STIM1). In vitro analyses showed that SOCE and Ag receptor complex-triggered Ca(2+) flux into STIM1-deficient T cells is virtually abolished. In vivo, STIM1-deficient mice developed a lymphoproliferative disease despite normal thymic T cell maturation and normal frequencies of CD4(+)Foxp3(+) regulatory T cells. Unexpectedly, STIM1-deficient bone marrow chimeric mice mounted humoral immune responses after vaccination and STIM1-deficient T cells were capable of inducing acute graft-versus-host disease following adoptive transfer into allogeneic hosts. These results demonstrate that STIM1-dependent SOCE is crucial for homeostatic T cell proliferation, but of much lesser importance for thymic T cell differentiation or T cell effector functions.
Beyersdorf
Niklas
N
Institute for Virology and Immunobiology, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, Germany.
Braun
Attila
A
Vögtle
Timo
T
Varga-Szabo
David
D
Galdos
Ronmy Rivera
RR
Kissler
Stephan
S
Kerkau
Thomas
T
Nieswandt
Bernhard
B
D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000276:immunology; D015220:Calcium Channels / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D000071737:Stromal Interaction Molecule 1; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015220:Calcium Channels; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1