Regulation of cutaneous malignancy by gammadelta T cells

M Girardi; D E Oppenheim; C R Steele; J M Lewis; E Glusac; R Filler; P Hobby; B Sutton; R E Tigelaar; A C Hayday

doi:10.1126/science.1063916

Regulation of cutaneous malignancy by gammadelta T cells

M Girardi
, D E Oppenheim
, C R Steele
, J M Lewis
, E Glusac
, R Filler
, P Hobby
, B Sutton
, R E Tigelaar
, A C Hayday

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

740 Citations (Scopus)

Abstract

The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

Original language	English
Pages (from-to)	605-9
Number of pages	5
Journal	Science
Volume	294
Issue number	5542
DOIs	https://doi.org/10.1126/science.1063916
Publication status	Published - 19 Oct 2001

Keywords

Amino Acid Sequence
Animals
Carcinogens
Cell Line
Cytotoxicity, Immunologic
Dimerization
Epidermis
Epithelial Cells
Histocompatibility Antigens Class I
Humans
Immunologic Surveillance
Ligands
Membrane Proteins
Mice
Mice, Inbred C57BL
Minor Histocompatibility Antigens
Molecular Sequence Data
NK Cell Lectin-Like Receptor Subfamily K
Protein Conformation
Protein Folding
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Antigen, T-Cell, gamma-delta
Receptors, Immunologic
Receptors, Natural Killer Cell
Recombinant Fusion Proteins
Reverse Transcriptase Polymerase Chain Reaction
Skin Neoplasms
T-Lymphocyte Subsets

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10.1126/science.1063916

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title = "Regulation of cutaneous malignancy by gammadelta T cells",

abstract = "The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.",

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author = "M Girardi and Oppenheim, \{D E\} and Steele, \{C R\} and Lewis, \{J M\} and E Glusac and R Filler and P Hobby and B Sutton and Tigelaar, \{R E\} and Hayday, \{A C\}",

year = "2001",

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doi = "10.1126/science.1063916",

language = "English",

volume = "294",

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T1 - Regulation of cutaneous malignancy by gammadelta T cells

AU - Girardi, M

AU - Oppenheim, D E

AU - Steele, C R

AU - Lewis, J M

AU - Glusac, E

AU - Filler, R

AU - Hobby, P

AU - Sutton, B

AU - Tigelaar, R E

AU - Hayday, A C

PY - 2001/10/19

Y1 - 2001/10/19

N2 - The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

AB - The localization of gammadelta T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking gammadelta cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex-related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d+ gammadelta cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.

KW - Amino Acid Sequence

KW - Animals

KW - Carcinogens

KW - Cell Line

KW - Cytotoxicity, Immunologic

KW - Dimerization

KW - Epidermis

KW - Epithelial Cells

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Immunologic Surveillance

KW - Ligands

KW - Membrane Proteins

KW - Mice

KW - Mice, Inbred C57BL

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KW - Molecular Sequence Data

KW - NK Cell Lectin-Like Receptor Subfamily K

KW - Protein Conformation

KW - Protein Folding

KW - Receptors, Antigen, T-Cell, alpha-beta

KW - Receptors, Antigen, T-Cell, gamma-delta

KW - Receptors, Immunologic

KW - Receptors, Natural Killer Cell

KW - Recombinant Fusion Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Skin Neoplasms

KW - T-Lymphocyte Subsets

U2 - 10.1126/science.1063916

DO - 10.1126/science.1063916

M3 - Article

C2 - 11567106

SN - 0036-8075

VL - 294

SP - 605

EP - 609

JO - Science

JF - Science

IS - 5542

ER -

Regulation of cutaneous malignancy by gammadelta T cells

Abstract

Keywords

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