Abstracts (complete list) - Wissenschaft Online

Romy Laugks, Patricia Schmidbauer, Bernhard Holzmann, Melanie Laschinger
ROLE OF LFA-1 ACTIVITY REGULATION IN CELL CYCLE
CONTROL OF PROLIFERATING T LYMPHOCYTES
The leukocyte specific integrin LFA-1 (αLβ2) is crutial in the interaction between T
lymphocytes and antigen-presenting cells. It is well established that LFA-1 needs to be
activated in order to bind ligands. However, the function of LFA-1 de-activation is not
completely understood. By the deletion of the cytoplasmic GFFKR motif of the αL
subunit in mouse germ line we previously generated a mouse mutant that locks LFA-1
in an inactive state (LFA-1d/d). The defect of LFA-1 de-activation leads to an impaired
de-adhesion from its ligand ICAM-1 on endothelial cells reflected in a reduced migration.
We found the antigen-specific proliferation of LFA-1d/d T cells to be dramatically
reduced. The analysis of interaction between LFA-1d/d T cells and antigen-presenting
dendritic cells exhibits the disability of T cells expressing LFA-1 in a constitutively active
state to de-adhere from dendritic cells. Furthermore, we observed a different cell cycle
profile of LFA-1d/d T cells compared to wildtype cells suggesting an influence of LFA-1
in early cell cycle control.
These data imply that LFA-1 de-activation is essential for cell cycle control during
antigen-specific proliferation and clonal expansion of naïve T lymphocytes.