A novel function-associated molecule related to non-MHC-restricted cytotoxicity mediated by activated natural killer cells and T cells

B. A. Garni-Wagner, A. Purohit, P. A. Mathew, M. Bennett, V. Kumar

Research output: Contribution to journalArticlepeer-review

235 Scopus citations

Abstract

NK cells and IL-2-propagated splenic T cells mediate non-MHC-restricted cytotoxicity. The molecules involved in this process are not well defined. We describe a novel 66-kDa cell surface molecule called 2B4 that is expressed on cells that mediate non-MHC-restricted cytotoxicity. All resting and rIL-2 cultured NK cells and a significant number of T cells cultured in high doses of rIL-2 are 2B4+. In fresh as well as cultured spleen cells, all non-MHC- restricted cytotoxicity is contained within the 2B4+ population. In addition to defining cells capable of non-MHC-restricted killing, the 2B4 molecule is also involved in modulation of their function. In the presence of anti-2B4, the lytic activity of cultured NK cells and non-MHC-restricted T cells against a wide variety of FcR- and FcR+ targets is greatly augmented. Anti- 2B4 is also able to transduce other signals in IL-2-activated NK cells such as IFN-γ secretion and granule exocytosis. In addition, 2B4+ T cells can specifically lyse the 2B4 hybridoma cells. Unlike many other activation and adhesion molecules (such as murine CD2, LFA-1, and CD16), 2B4 expression is restricted to cells that mediate NK-like killing. Conversely, highly activated T cells that do not express 2B4 do not mediate non-MHC-restricted killing. Together these data suggest that the 2B4 molecule is likely to be a part of a receptor complex or a component of signal-transducing complex on cells that mediate non-MHC-restricted killing.

Original languageEnglish
Pages (from-to)60-70
Number of pages11
JournalJournal of Immunology
Volume151
Issue number1
StatePublished - 1993

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