Harada M, Matsunaga K, Oguchi Y, Iijima H, Ito O, Tamada K, Kimura G, Nomoto K
Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Cancer Res. 1995 Dec 15;55(24):6146-51.
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.
我们研究了肠道相关淋巴组织（GALT）中的抗肿瘤免疫反应，GALT是众多饮食抗原的诱导耐受部位。将结肠26癌（C-26）接种到盲肠浆膜下间隙（i.c.）的小鼠比将C-26接种到侧腹皮下（s.c.）的小鼠肿瘤生长更快。此外，i.c.接种C-26的小鼠血清显示出更强的抑制活性，其血浆中转化生长因子的水平高于s.c.接种C-26的小鼠。我们还利用B7转染的P815肥大细胞瘤（B7/P815）评估了GALT中肿瘤特异性T细胞反应。与s.c.接种的B7/P815相比，i.c.接种的B7/P815的排斥反应延迟。s.c.接种B7/P815的小鼠引流腋窝淋巴结（LN）细胞在体外再刺激时表现出CD4+T细胞依赖性增殖反应，而i.c.接种B7/P815的小鼠引流肠系膜LN细胞即使添加白细胞介素2也无明显反应。然而，这种引流肠系膜LN细胞在没有任何刺激的情况下确实比引流腋窝LN产生更高水平的白细胞介素2和转化生长因子β，并且它们产生这些细胞因子分别依赖于CD4+和CD8+细胞。总的来说，我们的结果表明，GALT中抗肿瘤T细胞反应受损可能归因于产生TGF-β的CD8+T细胞的“旁观者抑制”。
