The involvement of transforming growth factor beta in the impaired antitumor T-cell response at the gut-associated lymphoid tissue (GALT).
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.
Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
M
M
Harada
K
K
Matsunaga
Y
Y
Oguchi
H
H
Iijima
O
O
Ito
K
K
Tamada
G
G
Kimura
K
K
Nomoto
D000818:Animals; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology*; D004731:Endotoxins / Q000097:blood; D005260:Female; D007108:Immune Tolerance; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007422:Intestines / Q000276:immunology*; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D012709:Serum Albumin / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*
D004731:Endotoxins; D012709:Serum Albumin; D016212:Transforming Growth Factor beta