Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10902-6. Epub 2003 Aug 28.

CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses.

Author information

1
Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.

Abstract

A variety of tumor-derived antigens have been defined by IgG antibodies in tumor bearers' sera with serological identification of antigens by recombinant expression cloning (SEREX), a serological expression cloning method. The majority of these antigens show no structural abnormality and seem to be wild-type autoantigens. Coimmunization with DNA encoding these autoantigens and tumor-specific cytotoxic T lymphocytes epitopes heightened CD8+ T cell responses and increased resistance to tumor challenge in a CD4+ T cell-dependent manner. In contrast, immunization with these SEREX-defined autoantigens alone leads to heightened susceptibility to tumor challenge. This suppressive effect of immunization is mediated by CD4+ CD25+ T cells. In mice immunized with one of the SEREX-defined autoantigens, Dna J-like 2, the number of alpha-GalCer/CD1d tetramer+ CD3+ T cells [representing natural killer T (NKT) cells] was reduced in the pulmonary compartment, whereas no evident change in the number of other T cell subsets was observed. Experiments with Jalpha281-/- mice lacking most NKT cells indicate that NKT cells are primarily responsible for metastasis suppression and that their activity is inhibited by immunization with Dna J-like 2. We propose that SEREX identifies a pool of autoantigens that maintains and regulates immunological homeostasis via CD4+ CD25+ regulatory T cells.

PMID:
12947044
PMCID:
PMC196900
DOI:
10.1073/pnas.1834479100
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center