Tumor-specific killer cells in paraneoplastic cerebellar degeneration

Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood 1 . Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mecha...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Nature Medicine Ročník 4; číslo 11; s. 1321 - 1324
Hlavní autoři:	Albert, Matthew L., Darnell, Jennifer C., Bender, Armin, Francisco, Loise M., Bhardwaj, Nina, Darnell, Robert B.
Médium:	Journal Article Magazine Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.11.1998 Nature Publishing Group
Témata:	Animals Apoptosis - radiation effects Biomedical and Life Sciences Biomedicine Breast Neoplasms - immunology Cancer Research Cells, Cultured Cerebellar Diseases - immunology Cytotoxicity, Immunologic Female HeLa Cells Histocompatibility Antigens Class I - immunology Humans Immunity, Cellular Immunology Infectious Diseases Killer Cells, Natural - immunology Life Sciences Lymphoid Tissue - immunology Metabolic Diseases Mice Molecular Medicine Nerve Degeneration - immunology Neurosciences Ovarian Neoplasms - immunology Paraneoplastic Syndromes - immunology T-Lymphocyte Subsets - immunology T-Lymphocytes, Cytotoxic - immunology Ultraviolet Rays
ISSN:	1078-8956, 1546-170X, 1744-7933
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood 1 . Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mechanisms underlying tumor immunity to breast and ovarian cancer. Although tumor immunity and autoimmune neuronal degeneration in PCD correlates with a specific antibody response to the tumor and brain antigen cdr2 2 , 3 , this humoral response has not been shown to be pathogenic 3 , 4 . Here we present evidence for a specific cellular immune response in PCD patients. We have detected expanded populations of MHC class I-restricted cdr2-specific CTLs in the blood of 3/3 HLA-A2.1 + PCD patients, providing the first description, to our knowledge, of tumor-specific CTLs using primary human cells in a simple recall assay. Cross-presentation of apoptotic cells by dendritic cells also led to a potent CTL response. These results indicate a model whereby immature dendritic cells that engulf apoptotic tumor cells can mature and migrate to draining lymph organs where they could induce a CTL response to tissue-restricted antigens. In PCD, peripheral activation of cdr2-specific CTLs is likely to contribute to the subsequent development of the autoimmune neuronal degeneration.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1078-8956 1546-170X 1744-7933
DOI:	10.1038/3315