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Umbilical Cord Blood T Cells Express Multiple Natural Cytotoxicity Receptors after IL-15 Stimulation, but Only NKp30 Is Functional¹

Qin Tang^*, Bartosz Grzywacz^*, Hongbo Wang^*, Nandini Kataria, Qing Cao, John E. Wagner^*, Bruce R. Blazar^*, Jeffrey S. Miller and Michael R. Verneris^2,*

^* Department of Pediatrics and Department of Medicine, Division of Blood and Marrow Transplantation, and Biostatistics Shared Resource, Cancer Center, University of Minnesota, Minneapolis, MN 55455

The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are thought to be NK lineage restricted. Herein we show that IL-15 induces NCR expression on umbilical cord blood (UCB) T cells. NCRs were mainly on CD8⁺ and CD56⁺ UCB T cells. Only NKp30 was functional as demonstrated by degranulation, IFN- release, redirected killing, and apoptosis. Since NCRs require adaptor proteins for function, the expressions of these adaptors were determined. The adaptors used by NKp30 and NKp46, FcR1 and CD3, were detected in UCB T cells. There was a near absence of DAP12, the adaptor for NKp44, consistent with a hypofunctional state. NKp46 was on significantly fewer UCB T cells, possibly accounting for its lack of function. Adult peripheral blood (PB) T cells showed minimal NCR acquisition after culture with IL-15. Since UCB contains a high frequency of naive T cells, purified naive T cells from adult PB were tested. Although NKp30 was expressed on a small fraction of naive PB T cells, it was nonfunctional. In contrast to UCB, PB T cells lacked FcR1 expression. These results demonstrate differences between UCB and PB T cells regarding NCR expression and function. Such findings challenge the concept that NCRs are NK cell specific.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Q.T. designed, performed, and analyzed experiments and wrote the paper. B.G. designed, performed, and analyzed experiments and wrote the paper. H.W. designed, performed, and analyzed experiments. N.K. designed, performed, and analyzed experiments. Q.C. performed statistical analyses. J.E.W. provided essential reagents, analyzed experiments, and contributed to the writing of the paper. B.R.B. designed experiments and contributed to the writing of the paper. J.S.M. designed experiments and contributed to the writing of the paper. M.R.V. designed and analyzed experiments and wrote the paper.

¹ This work was supported by Children’s Cancer Research Fund (to M.R.V.) and by National Institutes of Health Grants P01 CA65493 (to J.S.M.), R01 HL55417 (to J.S.M.), R01 AI34495 (to B.R.B.), and R01 CA72669 (to B.R.B.).

² Address correspondence and reprint requests to Dr. Michael R. Verneris, Suite 660, 425 East River Road, Minneapolis, MN 55455. E-mail address: Verneris{at}umn.edu

³ Abbreviations used in this paper: UCB, umbilical cord blood; AICD, activation-induced cell death; CM, central memory; EM, effector memory; KIR, killer Ig-like receptors; NCR, natural cytotoxicity receptor; PB, peripheral blood.

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