Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells.

Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells.

Blog Article

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.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 30hh bikini 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 bilstein shocks jeep xj 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.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.