RRC ID |
41422
|
著者 |
Seo N, Hayakawa S, Takigawa M, Tokura Y.
|
タイトル |
Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity.
|
ジャーナル |
Immunology
|
Abstract |
We investigated the relationship between transforming growth factor-beta (TGF-beta)-secreting T-regulatory (Tr) cells and anti-B16 melanoma immunity, and studied the association of early cytokines expressed at tumour sites with the generation of Tr cells. A large number of CD4(+) Tr cells producing interleukin (IL)-4, IL-10 and TGF-beta accumulated with functionally depressed CD8(+) cytotoxic T lymphocytes (CTLs) at tumour sites on day 20 after subcutaneous (s.c.) inoculation of B16 tumour cells. Tr cells consisted of two populations, which were termed T helper 3 (Th3) and Tr1 cells. B16-infiltrating Tr cells strongly inhibited the generation of B16-specific T helper 1 (Th1) cells in a TGF-beta-dependent manner and were assumed to suppress effective generation of CTLs. In addition, B16 cells markedly progressed in mice transferred adoptively by the cultured B16-infiltrating Tr cells compared with untreated mice. The capacity of these Tr cells to produce TGF-beta was hampered by neutralizing anti-IL-10 and partly anti-IL-4 monoclonal antibodies (mAbs) injected intralesionally during the early development of B16 tumours, and this treatment markedly attenuated B16 growth. Furthermore, a lesional injection of recombinant mouse IL-10 at an early tumour site resulted in the vigorous progression of B16 tumours. These results provide evidence that Tr cells, belonging to the T helper 3/T-regulatory 1 (Th3/Tr1) type, are activated in B16-bearing hosts under the influence of T helper 2 (Th2) cytokines, mainly IL-10 (produced at early tumour lesions), and that this regulatory T-cell population functions as a suppressor of anti-B16 immunity.
|
巻・号 |
103(4)
|
ページ |
449-57
|
公開日 |
2001-8-1
|
DOI |
10.1046/j.1365-2567.2001.01279.x
|
PII |
imm1279
|
PMID |
11529935
|
PMC |
PMC1783257
|
MeSH |
Animals
CD4-Positive T-Lymphocytes / immunology*
Cell Culture Techniques
Disease Progression
Down-Regulation / immunology
Female
Immune Tolerance*
Immunity, Cellular
Interleukin-10 / immunology*
Interleukin-10 / metabolism
Lymphocytes, Tumor-Infiltrating / immunology*
Melanoma, Experimental / immunology*
Mice
Mice, Inbred C57BL
T-Lymphocyte Subsets / immunology
Transforming Growth Factor beta / metabolism
|
IF |
5.016
|
引用数 |
152
|
WOS 分野
|
IMMUNOLOGY
|
リソース情報 |
ヒト・動物細胞 |
B16 melanoma 4A5(RCB0557) |