IMMUNOLOGICAL ASPECTS OF AGING

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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).