Stable long-term induction of perforin-positive CD8+ T cells in gut by oral administration of streptococcal preparation OK-432.
Perforin is known as a pore-forming cytotoxic granule released from cytotoxic T cells. Previous experiments in vitro revealed the presence of precursor cells that are capable of producing perforin in the immune system cells. The present study was undertaken to examine whether perforin-positive cells could be induced in the digestive tract and to characterize their precursor cells. Expression of perforin-positive cells in the intestine of Balb/c mice induced by OK-432 was analyzed by immunohistochemical staining and RT-PCR. Oral treatment of Balb/c mice with OK-432 resulted in the occurrence of perforin-positive cells in the inferior segment of small intestine, the superior segment of large intestine, mesenteric lymph nodes and spleen. In the small intestine, perforin-positive cells were found in the lamina propria mucosa. The presence of perforin-positive cells was also noted following long-term OK-432 treatment. Similar results were obtained following treatment with biological response modifiers such as lipopolysaccharide. In mice with GVHD (graft-versus-host disease), the presence of perforin-positive cells was noted in the small intestine and spleen. When the serial sections of the small intestinal mucosa from OK-432-treated mice were immunostained with anti-perforin, anti-CD8 and anti-asialo-GM1 antibodies, the perforin-positive cells were found to be CD8-positive. The results suggest that CD8(+) cells in lamina propria mucosa play a significant role as effectors in the mucosal immune system which is activated by various stimuli.
Mino
Norifumi
N
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, Okayama 700-8558, Japan.
Naomoto
Yoshio
Y
Shirakawa
Yasuhiro
Y
Matsuoka
Junji
J
Nobuhisa
Tetsuji
T
Gunduz
Mehmet
M
Noma
Kazuhiro
K
Nagatsuka
Hitoshi
H
Kobayashi
Masahiko
M
Yamatsuji
Tomoki
T
Haisa
Minoru
M
Gochi
Akira
A
Tanaka
Noriaki
N
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D054353:Perforin; D010844:Picibanil / Q000008:administration & dosage / Q000494:pharmacology*; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D010844:Picibanil