Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms.

J Immunol 2010 Jul 7;185(1):367-75. Epub 2010 Jun 7.

Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Australia.

Asymmetric cell division is a potential means by which cell fate choices during an immune response are orchestrated. Defining the molecular mechanisms that underlie asymmetric division of T cells is paramount for determining the role of this process in the generation of effector and memory T cell subsets. In other cell types, asymmetric cell division is regulated by conserved polarity protein complexes that control the localization of cell fate determinants and spindle orientation during division. We have developed a tractable, in vitro model of naive CD8(+) T cells undergoing initial division while attached to dendritic cells during Ag presentation to investigate whether similar mechanisms might regulate asymmetric division of T cells. Using this system, we show that direct interactions with APCs provide the cue for polarization of T cells. Interestingly, the immunological synapse disseminates before division even though the T cells retain contact with the APC. The cue from the APC is translated into polarization of cell fate determinants via the polarity network of the Par3 and Scribble complexes, and orientation of the mitotic spindle during division is orchestrated by the partner of inscuteable/G protein complex. These findings suggest that T cells have selectively adapted a number of evolutionarily conserved mechanisms to generate diversity through asymmetric cell division.

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.0903627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739982PMC
July 2010
28 Reads
49 Citations
4.922 Impact Factor

Publication Analysis

Top Keywords

division cells
16
cell division
16
asymmetric cell
16
cell fate
12
division
10
cell
8
conserved mechanisms
8
asymmetric division
8
fate determinants
8
cells
8
asymmetric
6
dendritic cells
4
cd8+ cells
4
naive cd8+
4
attached dendritic
4
model naive
4
mitotic spindle
4
spindle division
4
initial division
4
undergoing initial
4

Altmetric Statistics

Similar Publications