Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms.
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.
Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Australia.
Jane
J
Oliaro
Vanessa
V
Van Ham
Faruk
F
Sacirbegovic
Anupama
A
Pasam
Ze'ev
Z
Bomzon
Kim
K
Pham
Mandy J
MJ
Ludford-Menting
Nigel J
NJ
Waterhouse
Michael
M
Bots
Edwin D
ED
Hawkins
Sally V
SV
Watt
Leonie A
LA
Cluse
Chris J P
CJ
Clarke
David J
DJ
Izon
John T
JT
Chang
Natalie
N
Thompson
Min
M
Gu
Ricky W
RW
Johnstone
Mark J
MJ
Smyth
Patrick O
PO
Humbert
Steven L
SL
Reiner
Sarah M
SM
Russell
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002455:Cell Division / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism