The involvement of transforming growth factor beta in the impaired antitumor T-cell response at the gut-associated lymphoid tissue (GALT).
The involvement of transforming growth factor beta in the impaired antitumor T-cell response at the gut-associated lymphoid tissue (GALT).
复制标题
转化生长因子β参与肠道相关淋巴组织 (GALT) 抗肿瘤 T 细胞反应受损。
作者：
M. Harada;K. Matsunaga;Y. Oguchi;H. Iijima;O. Ito;K. Tamada;G. Kimura;K. Nomoto
我们研究了肠道相关淋巴组织(GALT)的抗肿瘤免疫反应，GALT是许多饮食抗原的耐受诱导部位。将小鼠结肠癌26(C-26)接种到盲肠浆膜下腔(I.C.)显示出比接种S.C.的小鼠更快的肿瘤生长。C-26进入侧翼。此外，I.C.的血清。接种C-26的小鼠表现出更强的抑制活性，它们的血浆中含有比SC更高的转化生长因子水平。C-26-接种小鼠。我们还利用B7转基因的P815肥大细胞瘤(B7/P815)来评估GALT中肿瘤特异性T细胞的反应。对I.C.的拒绝。接种B7/P815的时间比接种S.C.接种B7/P815。S.C.的引流腋窝淋巴结(LN)细胞。接种B7/P815的小鼠对体外再刺激表现出依赖于CD4+T细胞的增殖反应，而I.C.的肠系膜LN细胞引流。接种B7/P815的小鼠即使在加入白介素2的情况下也没有表现出明显的反应。然而，这种引流的肠系膜LN细胞确实比没有任何刺激的引流的腋窝LN细胞产生更高水平的白介素2和转化生长因子β，并且它们产生的细胞因子分别依赖于CD4+和CD8+细胞。总而言之，我们的结果提示GALT中抗肿瘤T细胞反应受损的可能性可能归因于产生转化生长因子-β的CD8+T细胞的“旁观者抑制”。
We studied the antitumor immune response in gut-associated lymphoid tissue (GALT), which is the tolerance-inducing site for numerous dietary antigens. The mice inoculated with colon 26 carcinoma (C-26) into the subserosal space of the cecum (i.c.) showed a more rapid tumor growth than did the mice inoculated s.c. with C-26 into the flank. In addition, the serum of the i.c. C-26-inoculated mice showed a more potent suppressive activity, and their plasma contained a higher level of transforming growth factor than the s.c. C-26-inoculated mice. We also evaluated the tumor-specific T-cell response in the GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The rejection of i.c. inoculated B7/P815 was delayed compared to that of the s.c. inoculated B7/P815. The draining axillary lymph node (LN) cells of the s.c. B7/P815-inoculated mice exhibited a CD4+ T-cell-dependent proliferative response to in vitro restimulation, whereas the draining mesenteric LN cells of the i.c. B7/P815-inoculated mice exhibited no apparent response even with the addition of interleukin 2. However, such draining mesenteric LN cells did produce higher levels of interleukin 2 and transforming growth factor beta than the draining axillary LN without any stimulation, and their production of such cytokines depend on the CD4+ and CD8+ cells, respectively. Collectively, our results suggest the possibility that the impaired antitumor T-cell response in the GALT may be attributed to "bystander suppression" by TGF-beta-producing CD8+ T cells.
影响因子：
56.9
作者：
TOWNSEND, SE;ALLISON, JP
通讯作者：
ALLISON, JP
DOI：
10.1073/pnas.89.1.421
发表时间：
1992-01-01
影响因子：
11.1
作者：
MILLER, A;LIDER, O;WEINER, HL
通讯作者：
WEINER, HL