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K Kishihara

Publications and source records attributed to K Kishihara.

78 records · Page 5Linked to original sources

Age-associated increase in the expression of T-cell antigen receptor gamma-chain gene in conventional and germfree mice.

To determine whether environmental antigens such as intestinal microflora contribute to expansion of the T-cell repertoire, age-related changes in the expression level of T-cell antigen receptor genes encoding gamma, beta, and alpha chains were compared in the lymphoid tissues of conventional versus germfree mice. Irrespective of the conditions of maintenance, an age-associated increase in the expression of the gamma-chain gene was evident in the thymus and spleen. Both conventional and germfree old mice (age, 40 weeks) had a relatively high proportion of Thy1+ L3T4- Lyt2- cells but a reduced level of Thy1+ L3T4- Lyt2+ cells in the thymus compared with their counterparts (age 8 weeks). The thymic dysfunction but not the stimulation by intestinal microflora may contribute to this age-related increase in gamma-gene transcripts in these tissues. On the other hand, an age-associated increase in the expression of gamma RNA was not evident in the mesenteric lymph nodes of germfree mice, although a remarkable increase in the gamma-chain gene messages was detected in the lymph nodes of the aged conventional mice. These results suggest that the expression of gamma RNA in cells of gut-associated lymphoid tissue is partly influenced by intestinal microflora.

Age Factors↗

Sequential appearance of thymocyte subpopulations and T cell antigen receptor gene messages in the mouse thymus after sublethal irradiation.

The sequential differentiation patterns of thymocyte were observed with cell surface phenotypes and the expression of T cell antigen receptor in 800 rad irradiated adult mice. Thymus was severely reduced in size and cell number by day 5 after whole body irradiation and rapidly recovered from day 7 to day 14. Surface marker analysis on day 5 after irradiation showed thymocytes with Thy-1low L3T4+/Lyt-2- dominantly existed and suggested that these cells were radioresistant-survived cells. On the other hand, thymocytes on day 7 were composed of a large number of Thy-1high L3T4+/Lyt-2+ blast-like cells and a relatively high proportion of Thy-1high L3T4-/Lyt-2- cells which expressed a large amount of gamma-chain gene messages but scarcely any alpha- and beta-chain gene messages similar to the fetal thymocytes. On day 14, thymocytes were composed mostly of Thy-1high H-2low L3T4+/Lyt-2+ subpopulation which expressed a remarkably low level of gamma-chain gene messages, and high levels of alpha- and beta-chain transcripts analogous to those of normal adult thymus. Taken together, intrathymic radioresistent stem cells for T thymocytes seem to proliferate and differentiate after irradiation with the same pattern as was seen in a fetal thymus development.

Animals↗

Functional alpha and beta T cell chain receptor messages can be detected in old but not in young athymic mice.

The expression and sequences of T cell antigen receptor (TcR) alpha and beta-chain genes were investigated in the spleens from congenitally athymic (nude) mice. A small number of Thy-1+ cells (approximately 7.0%) was found in nylon wool-enriched spleen cells from young (8 weeks old) nude mice but no L3T4 or Lyt-2 surface antigens were detected. These nude mice expressed only a low level of 1.0-kb beta-chain mRNA and little or no alpha-gene transcripts. On the other hand the number of Thy-1+ spleen cells increased slightly (to 24%) in old (20 weeks old) nude mice and a small number of L3T4+ (10%) and/or Lyt-2+ (5%) cells were detectable. "Full length" 1.7-kb alpha-chain and 1.3-kb beta-chain messages could be found in nylon wool-enriched spleen cells from old nude mice. Sequence analysis of the cDNA revealed that no functional alpha and beta-chain genes can be detected in the spleen cells of young athymic mice while some of the old mice with nu/nu genotype are composed of completely rearranged V-(D)-J-C-gene segments which encode potentially functional proteins. Interestingly, two of three independent cDNA clones encoding the alpha chain used the same V alpha and J alpha-gene segments. These results suggest that extrathymic TcR alpha and beta-chain gene rearrangements do occur, though slowly, to some extent, in nude mice and may be responsible for the limited antigen and/or H-2-related T cell functions in these old athymic mice. The data further suggests that the TcR repertoire in athymic mice may also be limited.

Age Factors↗

N-3 polyunsaturated fatty acids accentuate B16 melanoma growth and metastasis through suppression of tumoricidal function of T cells and macrophages.

BACKGROUND: The antitumor effects of the n-3 polyunsaturated fatty acids (PUFAs) are still controversial and as yet undefined. MATERIALS AND METHODS: EPA-28, a fish oil enriched with n-3 PUFAs including eicosapentaenoic and docosahexaenoic acids, was administered subcutaneously into C57BL/6 mice before and after subcutaneous inoculation of B16 melanoma cells. The effects of EPA-28 on the antitumor activities of T cells and macrophages were investigated. RESULTS: The treatment of the mice with EPA-28 before and after the tumor inoculation enhanced the growth and metastasis of B16 melanoma and decreased the survival rate of the tumor-bearing mice. The treatment also decreased the number of CD4+ T cells in the spleen and tumor draining lymph nodes on day 14 after the tumor inoculation. Moreover, EPA-28 suppressed the antimelanoma cytolytic activity of T cells and macrophages of the tumor-bearing mice. CONCLUSION: The results suggest that EPA-28 treatment increased both the growth and metastasis of B16 melanoma cells by suppressing the cytolytic function of both T cells and macrophages.

Animals↗