Journal Article

In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for <i>Cryptococcus neoformans</i> bypasses LFA-1

Gareth J. Jones, Jeremy C. D. Wiseman, Kaleb J. Marr, Sheng Wei, Julie Y. Djeu and Christopher H. Mody

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 21, issue 4, pages 423-432
Published in print April 2009 | ISSN: 0953-8178
Published online March 2009 | e-ISSN: 1460-2377 | DOI:
In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for Cryptococcus neoformans bypasses LFA-1

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NK cell cytotoxicity requires two positive signals for killing of tumors. Activation receptors induce polarization of the microtubule organization center and degranulation, while leukocyte function-associated antigen (LFA)-1 is required for conjugate formation and actin polymerization and under some circumstances may be sufficient for NK cell cytotoxicity. Although the receptor for direct killing of fungi is not known, CD18, the β2 chain of LFA-1, binds components of the capsule and cell wall of the opportunistic pathogen Cryptococcus neoformans, namely the polysaccharides glucoronoxylomannan and galactoxylomannan. Herein, we also demonstrate that LFA-1 was concentrated in regions of the NK cell surface interacting with C. neoformans. Consequently, there was compelling evidence to hypothesize that NK cells would also use LFA-1 to recognize and kill C. neoformans. Using a combination of NK cell lines that did or did not express LFA-1 or by using a CD18-specific functional blocking antibody, we confirm that NK cell anti-tumor activity is critically dependent upon the expression of LFA-1. Duplicating the events of tumor cytotoxicity, NK cells form conjugates with cryptococcal targets, rearrange the cell cytoskeleton to develop an NK immunologic synapse and release perforin-containing granules; however, each of these events occurred independently of LFA-1. Furthermore, NK cell-mediated killing of C. neoformans was detectable in both NK cells pre-treated with CD18-blocking antibodies and in NK cells lacking cell surface LFA-1 expression. These results demonstrate that in the absence of LFA-1 expression, NK cells are fully capable of recognizing a target (C. neoformans) and retain all of the events required for cytotoxicity.

Keywords: cytotoxicity; fungal; NK cells

Journal Article.  5874 words.  Illustrated.

Subjects: Biological Sciences ; Immunology

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