Calpain 4 Is Not Necessary for LFA-1-Mediated Function in CD4+T Cells

被引:4
作者
Wernimont, Sarah A. [1 ]
Simonson, William T. N. [1 ]
Greer, Peter A. [2 ]
Seroogy, Christine M. [3 ,4 ]
Huttenlocher, Anna [3 ,4 ]
机构
[1] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53706 USA
[2] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada
[3] Univ Wisconsin, Dept Pediat, Madison, WI USA
[4] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI USA
来源
PLOS ONE | 2010年 / 5卷 / 05期
基金
美国国家卫生研究院;
关键词
PERIPHERAL T-CELLS; UBIQUITOUS CALPAINS; CYTOPLASMIC DOMAIN; ACTIVATION; LFA-1; APOPTOSIS; MIGRATION; DEATH; DISRUPTION; INHIBITORS;
D O I
10.1371/journal.pone.0010513
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: T cell activation and immune synapse formation require the appropriate activation and clustering of the integrin, LFA-1. Previous work has reported that the calpain family of calcium-dependent proteases are important regulators of integrin activation and modulate T cell adhesion and migration. However, these studies have been limited by the use of calpain inhibitors, which have known off-target effects. Methodology/Principal Findings: Here, we used a LoxP/CRE system to specifically deplete calpain 4, a small regulatory calpain subunit required for expression and activity of ubiquitously expressed calpains 1 and 2, in CD4+ T cells. CD4+ and CD8+ T cells developed normally in Capn4(F/F): CD4-CRE mice and had severely diminished expression of Calpain 1 and 2, diminished talin proteolysis and impaired casein degradation. Calpain 4-deficient T cells showed no difference in adhesion or migration on the LFA-1 ligand ICAM-1 compared to control T cells. Moreover, there was no impairment in conjugation between Capn4(F/F):CD4-CRE T cells and antigen presenting cells, and the conjugates were still capable of polarizing LFA-1, PKC-theta and actin to the immune synapse. Furthermore, T cells from Capn4(F/F):CD4-CRE mice showed normal proliferation in response to either anti-CD3/CD28 coated beads or cognate antigen-loaded splenocytes. Finally, there were no differences in the rates of apoptosis following extrinsic and intrinsic apoptotic stimuli. Conclusion/Significance: Our findings demonstrate that calpain 4 is not necessary for LFA-1-mediated adhesion, conjugation or migration. These results challenge previous reports that implicate a central role for calpains in the regulation of T cell LFA-1 function.
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页数:9
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