Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection

Janice M Kelly; Phillip K Darcy; Jessica L Markby; Dale I Godfrey; Kazuyoshi Takeda; Hideo Yagita; Mark J Smyth

doi:10.1038/ni746

Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection

Nat Immunol. 2002 Jan;3(1):83-90. doi: 10.1038/ni746. Epub 2001 Dec 17.

Authors

Janice M Kelly¹, Phillip K Darcy, Jessica L Markby, Dale I Godfrey, Kazuyoshi Takeda, Hideo Yagita, Mark J Smyth

Affiliation

¹ Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria, Australia.

PMID: 11743585
DOI: 10.1038/ni746

Abstract

Natural killer (NK) cells may modulate the development of adaptive immune responses, but until now there has been little evidence to support this hypothesis. We investigated the primary and secondary immunity elicited by various tumor cell lines that express CD70 and interact with CD70 ligand (CD27), which is constitutively expressed on NK cells. CD70 expression enhanced primary tumor rejection in vivo as well as T cell immunity against secondary tumor challenge. Primary rejection of major histocompatibility complex (MHC) class I-deficient RMA-S.CD70 tumor cells was mediated by NK cells and perforin- and interferon-gamma-dependent mechanisms. This NK cell-mediated process also efficiently evoked the subsequent development of tumor-specific cytotoxic and T helper type 1 responses to the parental, MHC class I-sufficient, RMA tumor cells. Thus CD27-CD70 interactions provide a key link between innate NK cell responses and adaptive T cell immunity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD*
CD27 Ligand
Graft Rejection / immunology*
Homeodomain Proteins / genetics
Homeodomain Proteins / physiology
Immunologic Memory*
Interferon-gamma / physiology
Killer Cells, Natural / immunology*
Lymphoma, T-Cell / immunology*
Lymphoma, T-Cell / pathology
Membrane Glycoproteins / physiology
Membrane Proteins / immunology*
Mice
Mice, Knockout
Models, Immunological
Neoplasm Transplantation / immunology
Perforin
Pore Forming Cytotoxic Proteins
T-Lymphocyte Subsets / immunology*
T-Lymphocytes, Cytotoxic / immunology
Th1 Cells / immunology
Thymus Neoplasms / immunology*
Thymus Neoplasms / pathology
Tumor Cells, Cultured / transplantation
Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*

Substances

Antigens, CD
CD27 Ligand
Cd70 protein, mouse
Homeodomain Proteins
Membrane Glycoproteins
Membrane Proteins
Pore Forming Cytotoxic Proteins
Tumor Necrosis Factor Receptor Superfamily, Member 7
Perforin
RAG-1 protein
Interferon-gamma