Regulation of immunological disorders by invariant Vα19-Jα33 TCR-bearing cells.
We have previously shown that over-expression of the invariant Vα19-Jα33 TCR α transgene (Tg) using a natural TCR α promoter in mice induces the development of NK1.1(+) T cells (Vα19 NKT cells) in lymphoid organs, including the liver and intestine. These cells produce different spectra of immunoregulatory cytokines such as IL-4, IL-10, IL-17, and IFN-γ depending on the duration and intensity of the invariant TCR stimulation. In this study, we examined the effects of over-expression of invariant Vα19-Jα33 TCR-bearing cells on disease progress in the models of immunological disorders. The introduction of invariant Vα19 TCR Tg into non-obese diabetic mice delayed the onset of the disease. In addition, delayed-type hypersensitivity (DTH) to sheep erythrocytes was suppressed in the Vα19 Tg mice. DTH was also suppressed in the wild type mice previously transferred with Vα19 Tg(+) but not non-Tg cells. Thus, invariant Vα19 TCR-bearing cells are suggested to participate in the homeostasis of immunity to suppress disease progression resulting from Th1-immunity excess.
Shimamura
Michio
M
Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. michio@chem.tsukuba.ac.jp
Huang
Yi-Ying
YY
Goji
Hiroshi
H
Endo
Shin
S
Migishima
Rika
R
Yokoyama
Minesuke
M
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology; D019673:Genes, T-Cell Receptor alpha; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism
D000950:Antigens, Ly; D016207:Cytokines; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta