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Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation

Lui-Roberts, W.; Stinchcombe, J.C.; Ritter, A.T.; Akhmanova, A.; Karakesisoglou, I.; Griffiths, G.M.

Authors

W. Lui-Roberts

J.C. Stinchcombe

A.T. Ritter

A. Akhmanova

G.M. Griffiths



Abstract

Cytotoxic T lymphocytes (CTLs) kill tumorigenic and virally infected cells by targeted secretion of lytic granule contents. The precise point at which secretion occurs is directed by the centrosome docking at the immunological synapse (IS). The centrosome is highly dynamic in CTLs, lagging behind the nucleus in the uropod of migrating CTLs, but translocating across the entire length of the cell to dock at the IS when a target cell is recognized. While in most cell types, the centrosome is always closely associated with the nuclear membrane, in CTLs, it often appears to be dissociated from the nucleus, both in migrating cells and when forming an IS. We asked whether this dissociation is required for CTL killing, by expressing GFP-BICD2-NT-nesprin-3, which tethers the centrosome to the nucleus irreversibly. Immunofluorescence microscopy revealed that the centrosome polarized successfully to the central supramolecular activation complex (cSMAC) of the synapse in GFP-BICD2-NT-nesprin-3-expressing CTLs, with the centrosome and nucleus migrating together to the IS. CTLs in which the centrosome was “glued” to the nucleus were able to dock and release granules at the IS as effectively as mock-treated cells. These data demonstrate that CTL cytotoxicity is independent of centrosomal dissociation from the nuclear envelope.

Citation

Lui-Roberts, W., Stinchcombe, J., Ritter, A., Akhmanova, A., Karakesisoglou, I., & Griffiths, G. (2012). Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation. European Journal of Immunology, 42(8), 2132-2141. https://doi.org/10.1002/eji.201242525

Journal Article Type Article
Acceptance Date May 16, 2012
Publication Date 2012-08
Deposit Date May 14, 2012
Journal European Journal of Immunology
Print ISSN 0014-2980
Electronic ISSN 1521-4141
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 42
Issue 8
Pages 2132-2141
DOI https://doi.org/10.1002/eji.201242525
Keywords Centrosome, Cytotoxic T lymphocytes, Immunological synapse, Nucleus, Polarization.