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T cell– and B cell–independent adaptive immunity mediated by natural killer cells

Nature Immunology volume 7, pages 507–516 (2006)Cite this article

Abstract

It is commonly believed that only T lymphocytes and B lymphocytes expressing recombination-dependent antigen-specific receptors mediate contact hypersensitivity responses to haptens. Here we found that mice devoid of T cells and B cells demonstrated substantial contact hypersensitivity responses to 2,4-dinitrofluorobenzene and oxazolone. Those responses were adaptive in nature, as they persisted for at least 4 weeks and were elicited only by haptens to which mice were previously sensitized. No contact hypersensitivity was induced in mice lacking all lymphocytes, including natural killer cells. Contact hypersensitivity responses were acquired by such mice after adoptive transfer of natural killer cells from sensitized donors. Transferable hapten-specific memory resided in a Ly49C-I+ natural killer subpopulation localized specifically in donor livers. These observations indicate that natural killer cells can mediate long-lived, antigen-specific adaptive recall responses independent of B cells and T cells.

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Figure 1: Hapten-induced DTH response in mouse bladder.
Figure 2: Hapten-induced CHS responses in ears of wild-type and Rag2−/− mice.
Figure 3: NK cell accumulation in ears of DNFB-sensitized mice versus DNFB-sensitized and challenged mice.
Figure 4: NK cells are needed to mediate CHS responses in T cell– and B cell–deficient mice.
Figure 5: Differential CHS responses of mutant mouse strains to OXA and picryl chloride.
Figure 6: A subset of hepatic NK cells carries DNFB-specific memory in sensitized Rag2−/− mice.
Figure 7: NK receptors in CHS.
Figure 8: Function of adhesion molecules and NKG2D in CHS responses in Rag2−/− mice.

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Acknowledgements

We thank G. Cheng and B. Reinhardt for technical assistance; P. Schaerli for assistance in the design of ear sheet culture experiments; J. Lieberman, K. Rajewsky, F. Alt, D. Mathis and D. Podolsky for critical reading of the manuscript; and F. Alt for providing some of the Rag2−/− mice used. Supported by the American Association for the Study of Liver Diseases (J.G.O.) and the National Institutes of Health (AI061663, HL56949 and AR42689 to U.H.v.A.; T32 DK007191 to J.G.O.; T32 HL066987 to M.G.; and T32 AR07098-31 to D.L.D.).

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  1. Jacqueline G O'Leary, Mahmoud Goodarzi and Danielle L Drayton: These authors contributed equally to this work.

Authors and Affiliations

  1. The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Jacqueline G O'Leary, Mahmoud Goodarzi, Danielle L Drayton & Ulrich H von Andrian

  2. Department of Medicine, Harvard Medical School and Gastrointestinal Unit, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Jacqueline G O'Leary

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O'Leary, J., Goodarzi, M., Drayton, D. et al. T cell– and B cell–independent adaptive immunity mediated by natural killer cells. Nat Immunol 7, 507–516 (2006). https://doi.org/10.1038/ni1332

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