The Journal of Immunology, Vol 153, Issue 12 5473-5481, Copyright © 1994 by American Association of Immunologists

ARTICLES

CD44 is a cytotoxic triggering molecule in human peripheral blood NK cells

G Sconocchia, JA Titus and DM Segal
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.

Previous studies have shown that target cells that bind to CD44 adhesion molecules on cloned cytotoxic T cells are lysed by the CTL. To determine whether CD44 is also a cytotoxic trigger molecule in human PBL, we tested a bispecific Ab consisting of anti-CD44 Fab cross-linked to a Fab against a target cell Ag, in cytotoxicity assays using PBL as effectors. We found that PBL mediated lysis in the presence of the anti- CD44 bispecific Ab provided that the effector cells were stimulated with either IL-2 or IL-12. Cell fractionation experiments showed that CD44-directed cytolysis was mediated exclusively by CD56+ low buoyant density cells, mainly by NK (CD16+) cells, but also to a lesser extent by CD56+ T cells. CD44-directed cytolysis appeared in these subsets 24 to 48 h after addition of IL-2 and paralleled the acquisition of Ab- independent (LAK) activity; in contrast, these cells mediated Ab- dependent cellular cytotoxicity and CD3 redirected lysis before stimulation with IL-2. Unstimulated CD56+ cells uniformly expressed high levels of CD44 that increased modestly after incubation with IL-2. No changes in isoform expression in the extracellular domain of CD44 could be detected upon activation with the use of isoform-specific mAbs. Thus, lymphokine stimulation caused CD44 to become a cytotoxic trigger in subsets of PBL that mediated other forms of cytotoxicity and expressed CD44 before activation, suggesting that activation of these cells was accompanied by a coupling of CD44 to their lytic machinery.

This article has been cited by other articles:

				L. S. Shahied, Y. Tang, R. K. Alpaugh, R. Somer, D. Greenspon, and L. M. Weiner Bispecific Minibodies Targeting HER2/neu and CD16 Exhibit Improved Tumor Lysis When Placed in a Divalent Tumor Antigen Binding Format J. Biol. Chem., December 24, 2004; 279(52): 53907 - 53914. [Abstract] [Full Text] [PDF]

				A. I. Khan, S. M. Kerfoot, B. Heit, L. Liu, G. Andonegui, B. Ruffell, P. Johnson, and P. Kubes Role of CD44 and Hyaluronan in Neutrophil Recruitment J. Immunol., December 15, 2004; 173(12): 7594 - 7601. [Abstract] [Full Text] [PDF]

				S. Deaglio, M. Zubiaur, A. Gregorini, F. Bottarel, C. M. Ausiello, U. Dianzani, J. Sancho, and F. Malavasi Human CD38 and CD16 are functionally dependent and physically associated in natural killer cells Blood, April 1, 2002; 99(7): 2490 - 2498. [Abstract] [Full Text] [PDF]

				G. Sconocchia, L. Campagnano, D. Adorno, A. Iacona, N. Y. Cococcetta, V. Boffo, S. Amadori, and C. U. Casciani CD44 ligation on peripheral blood polymorphonuclear cells induces interleukin-6 production Blood, June 1, 2001; 97(11): 3621 - 3627. [Abstract] [Full Text] [PDF]

				A. M. McCall, L. Shahied, A. R. Amoroso, E. M. Horak, H. H. Simmons, U. Nielson, G. P. Adams, R. Schier, J. D. Marks, and L. M. Weiner Increasing the Affinity for Tumor Antigen Enhances Bispecific Antibody Cytotoxicity J. Immunol., May 15, 2001; 166(10): 6112 - 6117. [Abstract] [Full Text] [PDF]

				L. L. Lanier Turning On Natural Killer Cells J. Exp. Med., April 10, 2000; 191(8): 1259 - 1262. [Full Text] [PDF]

				G. Sconocchia, J. A. Titus, A. Mazzoni, A. Visintin, F. Pericle, S. W. Hicks, F. Malavasi, and D. M. Segal CD38 Triggers Cytotoxic Responses in Activated Human Natural Killer Cells Blood, December 1, 1999; 94(11): 3864 - 3871. [Abstract] [Full Text] [PDF]

				A. Q. Rafi, A. Zeytun, M. J. Bradley, D. P. Sponenberg, R. L. Grayson, M. Nagarkatti, and P. S. Nagarkatti Evidence for the Involvement of Fas Ligand and Perforin in the Induction of Vascular Leak Syndrome J. Immunol., September 15, 1998; 161(6): 3077 - 3086. [Abstract] [Full Text] [PDF]

				S. Ilangumaran, A. Briol, and D. C. Hoessli CD44 Selectively Associates With Active Src Family Protein Tyrosine Kinases Lck and Fyn in Glycosphingolipid-Rich Plasma Membrane Domains of Human Peripheral Blood Lymphocytes Blood, May 15, 1998; 91(10): 3901 - 3908. [Abstract] [Full Text] [PDF]

				G. Sconocchia, J. A. Titus, and D. M. Segal Signaling Pathways Regulating CD44-Dependent Cytolysis in Natural Killer Cells Blood, July 15, 1997; 90(2): 716 - 725. [Abstract] [Full Text] [PDF]

				S.-N. Zhu, B. Nolle, and G. Duncker Expression of adhesion molecule CD44 on human corneas Br. J. Ophthalmol., January 1, 1997; 81(1): 80 - 84. [Abstract] [Full Text] [PDF]