IMMUNOLOGICAL ASPECTS OF AGING

寿命受多种基因、性别和环境因素的影响。 环境因素的影响可以通过使用标准来最小化 情况，包括一年内的出生日期。遗传因素 可以使用特定染色体上不同的同源小鼠进行研究 区域，例如，在第4或第17染色体上。许多表型变化 随着年龄的增长而发生；我们感兴趣的是那些影响免疫力的因素 系统。我们建议测试正在进行的研究表明H-2d单倍型 与抵抗淋巴瘤和维持T细胞免疫有关 活力，以及H-2和4号染色体b位点附近基因影响 自然杀戮。我们还希望探索影响H-2基因的 寿命位于H-2单倍型的D端。此外，H-2 H-2的末端控制对淋巴瘤以及NK和T细胞的耐药性 功能。我们将使用几种实验模型：A)B10D2N、B10BR、B10 以及它们之间的杂交，以研究H-2与发病率的关系 淋巴瘤、T细胞功能和自然杀伤。B)B10D2N、B10、( B10D2NxB10BR)F1和(B10D2NxB10)F1逆转录病毒的表达 利用RNA杂交的Northern blotts序列能够预测 不同H-2单倍型小鼠中淋巴瘤的发生和c)我们将 正常脾淋巴细胞和淋巴组织中I类基因产物的比较 有淋巴瘤的结节。D)比较寿命、肿瘤发病率和NK 在Bailey的Hw26c和C57BL/6上的功能。这些遗传基因的不同之处仅在于 4号染色体的小区域，用b标记(Hw26c具有C57BL/6背景 和Balb/c染色体4的一部分)。E)我们提案的第二部分 打算绘制H-2对寿命、T细胞功能和 利用几种基因小鼠研究H-2基因D端淋巴瘤的发生率 H-2等位基因的组合。例如，B10.A(H-2a)和B10.A(5R) H-2I5仅在H-2和B10的k端不同，A在D端不同 B10.A(2R)。

Life span is influenced by several genes, sex and by environmental factors. The impact of environmental factors can be minimized by using standard conditions including the dated birth during the year. The genetic factors can be studied using congenic mice differing at specific chromosomal regions, e.g., on the 4th or 17th chromosomes. Many phenotypic changes occur with age; those we are interested in are those affecting the immune system. We propose to test ongoing studies suggesting that H-2d haplotype is associated with resistance to lymphomas and maintenance of T cell immune vigor, and that genes within H-2 and near b locus of chromosome 4 influence natural killing. We also wish to probe that the H-2 genes that influence life span are located in the D end of the H-2 haplotype. Also that the H-2 end of the H-2 controls resistance to lymphomas and both NK and T cell functions. We will use several experimental models: a) B10D2N, B10BR, B10 and hybrids among them to study the relationship between H-2 and incidence of lymphomas, T cell functions and natural killing. b) B10D2N, B10, ( B10D2NxB10BR)F1 and (B10D2NxB10)F1 to study the expression of retroviruses sequences using RNA hybridization Northern blots to be able to predict the occurrence of lymphomas in mice of different H-2 haplotypes and c) We will compare Class I gene products in normal lymphocytes of spleen and lymph nodes with lymphomas. d) Compare life span, incidence of tumors and NK functions in Hw26c and C57BL/6 of Bailey. These congenics differ only in a small region of chromosome 4 marked by b (The Hw26c have C57BL/6 background and part of chromosome 4 of Balb/c). e) The second part of our proposal intends to map the H-2 influence in life span, T cell function and incidence of lymphomas in the D end of H-2 using several congenics mice with combinations of H-2 alleles. For example, B10.A(H-2a) and B10.A(5R) H-2i5 differ only in the k end of H-2, and B10.A differ at D end of B10.A(2R).