Self-reactive T cell receptor-reactive CD8+ T cells inhibit T cell lymphoma growth in vivo.

Abstract

Syngenic C57BL/6 mice (H-2(b)) vaccinated with mitomycin C-treated L12R4 T lymphoma cells develop protective immunity toward the MHC class II-negative tumor cells. In the present study, we characterize the nature, mode of function, and specificity of the effector cells in this immunity. These cells are TCR-specific CD8(+) T lymphocytes with effector function in vitro as well as in vivo upon transfer to naive mice. They produce high levels of IFN-gamma and TNF-alpha, but little or no IL-4. By means of TCRbeta-negative variant L12R4 cells, P3.3, and TCR-Vbeta2 cDNA-transfected and TCR-Vbeta2-expressing P3.3 lymphoma cells, we found that a significant part of the effector T cells are specific for the Vbeta12 region. The growth inhibition of L12R4 cells in vitro was inhibited by anti-H-2, anti-K(b), and anti-D(b) mAb. Furthermore, vaccination with Vbeta12 peptide p67-78, which binds to both K(b) and D(b) MHC class I molecules, induces partial protection against L12R4 T lymphoma cells. Thus, self-reactive TCR-Vbeta-specific, K(b)-, or D(b)-restricted CD8(+) T cells mediate inhibition of T cell lymphoma growth in vitro and in vivo.

• Authors: Marie Gonthier, Régine Llobera, Jacques Arnaud, Bent Rubin
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 11 Pg. 7062-9 (Dec 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15557204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Epitopes, T-Lymphocyte
• Immunodominant Epitopes
• Receptors, Antigen, T-Cell, alpha-beta
• Interferon-gamma

Topics

• Amino Acid Sequence
• Animals
• Autoantigens (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism, transplantation)
• Cell Line, Tumor
• Cell Proliferation
• Cytotoxicity Tests, Immunologic
• Cytotoxicity, Immunologic
• Epitopes, T-Lymphocyte (immunology)
• Immunity, Innate
• Immunodominant Epitopes (immunology, metabolism)
• Immunotherapy, Adoptive (methods)
• Interferon-gamma (deficiency, genetics, physiology)
• Leukemia L1210
• Lymphoma, T-Cell (immunology, pathology, prevention & control)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Sequence Data
• Neoplasm Transplantation
• Receptors, Antigen, T-Cell, alpha-beta (immunology, metabolism)
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Regulatory (immunology)