| Co-Investigator(Kenkyū-buntansha) |
NODA Satoshi Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (10297260)
KATO Shunichi Tokai University, School of Medicine, Professor, 医学部, 教授 (70096212)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Animal model : When the BALB/c mice bred under SPF condition were intra-peritoneally infected with 0.2LD50 of murine cytomegalovirus (MCMV), high frequencies of CD69^+/CD44^+ MCMV-specific CD8 T cells were noted in the lungs even at 6 to 12 months after infection (11.1±3.2% and 9.8±0.9%, respectively). In contrast, even though the viral load and expression levels of mRNA of such cytokines as IL-2, IL-7, IL-15 and IFN-γ in the lungs of MCMV-infected OF mice were comparable to those of infected SPF mice, the frequencies of MCMV-specific CD8 T cells in the lungs of infected GF mice were kept lower than 1% at 6 to 12 months after infection. In addition, the reconstitution of microbiota of MCMV-infected GF mice by orally administering a fecal suspension prepared from SPF mice restored both the frequencies of CD8^+/multimer^+ and CD8^+/multimer T cells to levels similar to those found in SPF mice. These results suggested the indigenous microbiota to play a crucial role in the expansion and m
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aintenance of viral specific CD8 memory T cells, probably by cross-reactivity between the antigenic epitope of the MCMV-specific memory T cells and the variety of peptides derived from the members of the microbiota. Such cross-reactivity may thus be a major feature of those cells. Then, we examined to adoptive transfer of the MCMV-specific CD8^+/multimer^+ memory T cells for the treatment of CMV disease, At first, we tried to in vitro expand the MCMV-specific CD8^+/multimer^+ memory T cells, by co-culture with the memory T cells with the antigen-pulsed dentritic cells and such cytokines as IL-2 and /or IL-15. However, we could not in vitro expand the memory T cells under this culture condition.
Experiments using human materials : CMV-specific memory T cells were obtained from 20 volunteers, and then in vitro expansion of the memory T cells was done by co-culture with the memory T cells with the antigen-pulsed dentritic cells and IL-2. Memory T cells from the volunteer, who possessed the high frequency of CMV-specific memory T cells (>0.2% of total CD8 cells), could be adequately expanded. However, CMV-specific memory T cells form the other volunteers could not be expanded. Less
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