SHIRAI Toshikazu Department of Pathology, Juntendo University, School of Medicine, 医学部, 教授 (06404024)
TSURUI Hiromichi Department of Pathology, Juntendo University, School of Medicine
白井 俊一 順天堂大学, 医学部, 教授 (30115860)
鶴井 博理 順天堂大学, 医学部, 助手 (40217386)
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¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
CD45 is a family of membrane-integral protein tyrosine phosphatase thought to be involved in the regulation of signal transduction in lymphocyte. Outer-membrane domain of the molecule has three alternative structures, and eight isoforms are generated by the alternative splicing of exons 4,5 and 6. We analyzed the differential expression of tree CD45 alternative structures (CD45RA,B and C) of mouse CD45 in relation to the ontogeny and differentiation of lymphocyte subsets. The results are summarized as follows
B cells : While peripheral B cells were all CD45RA+B+C+, there were differential expressions of these epitopes on bone marrow B lineage cells. Although three alternative CD 45 epitopes began to be expressed at an early stage of pre B cells, the process of each epitope expression differed ; while the expression of CD45RA and CD45RC nearly coincided, CD45RB expression was markedly delayd. Since all three alternative CD45 mRNA expressions occurred at an early pre B cell stage, and pro
gressively elevated in subsequent developmental stages, the observed delay in the CD45RB expression appeared to be due to post-translational events
CD4+ T cells : Splenic CD4+ T cells included two populations, CD45RA-B+C- and CD45RA-B+C+. In these cells, messages of alternative exons were associated with either Bone (exon 4 or exon 5) or two exon form (exon 5 and exon 6) of the CD45 transcript.
When stimulated by an immobilized CD3 mAb, the CD45RC+CD4+ T cells secreted IL-2 but not other cytokines such as IL-4, IFN-g or IL-10, thereby represented "naive" ThP-type cells. CD45RC-CD4+ T cells produced IL-2, IL-4, IFN-g and IL-10 and likely included both Th1- and Th2-type cells.
CD8+ T cells : Splenic CD8+ T cells were separated into CD45RA-B+C+ and CD45RA+B+C+. There were transcripts with one, two, or three alternative exons suggesting that these cells express various types of CD45 isoforms including the largest form with all three alternative structures. Studies on T cell clones established in vitro revealed that while cytotoxic CD8+ T cells clones were CD45RA+, suppressor effecter CD8+ T cell clones were CD45RA-. Further studies on the functional difference between CD45RA-CD8+ T cells and CD45RA+CD8+ T cells are in progress. Less