Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.3/88512

Title

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

Author(s)

Oliaro, Jane;  Van Ham, Vanessa;  Sacirbegovic, Faruk;  Pasam, Anupama;  Bomzon, Ze'ev;  Pham, Kim;  Ludford-Menting, Mandy J.;  Waterhouse, Nigel J.;  Bots, Michael;  Hawkins, Edwin D.;  Watt, Sally V.;  Cluse, Leonie A.;  Clarke, Chris J. P.;  Izon, David J.;  Chang, John T.;  Thompson, Natalie;  Gu, Min;  Johnstone, Ricky W.;  Smyth, Mark J.;  Humbert, Patrick O.;  Reiner, Steven L.;  Russell, Sarah M.

Abstract

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.

Publication type

Journal article

Source

Journal of Immunology, Vol. 185, no. 1 (Jul 2010), pp. 367-375

Publication year

2010

FOR Code(s)

020503 Nonlinear Optics and Spectroscopy;  060111 Signal Transduction;  1107 Immunology;  110704 Cellular Immunology

Keyword(s)

APCs;  Asymmetric cell division;  T cells

Publisher

American Association of Immunologists

ISSN

0022-1767

Publisher URL

http://dx.doi.org/10.4049/jimmunol.0903627

Copyright

Copyright © 2010 by The American Association of Immunologists, Inc. The publisher does not allow institutions to archive either the accepted manuscript or the published version of the article.

Additional information

The authors acknowledge support from the National Health and Medical Research Council, Human Frontier Science Program, and the Australian Research Council.

Peer reviewed