We plan continued studies of the cellular and molecular biology of lymphocytes utilizing the approaches of cellular immunology, immunochemistry, and molecular genetics. The role of IL-4 in the immune response will be further evaluated with particular emphasis on the molecular mechanisms underlying the IL-4 induction of isotype switching to IgG1. Thus, after defining the critical biological parameters, these studies will involve analysis of changes in chromatin structure, sterile RNA transcripts, determination of promoter and enhancer sequences important in the switch, cloning of such sequences and characterization of the proteins that bind specifically to such sequences. The development of the antibody repertoire in humans will be analyzed by examining the usage of different VH subgroups in different types of lymphoid tissues. This will extend recent findings of a major difference in VH usage between blood and myeloma cells. The organization of human VH genes will be further analyzed because it differs significantly from that of the mouse. The role of T cell-T cell interactions in the generation of cytotoxic T lymphocytes will also be analyzed. The regulation of the generation of CTLs will be studied with particular emphasis on the role of CD4 positive cells as """"""""veto"""""""" cells. The maturation of T cells in epithelial tumors of the thymus and transplantable epithelial tumors of the salivary gland will allow analysis of in vitro and in vivo microenvironments and their impact on T cells with regard to induction of tolerance and immune responsiveness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI011851-19
Application #
3091429
Study Section
Allergy & Clinical Immunology-1 (AITC)
Project Start
1974-03-01
Project End
1994-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Harrod, F A; Hoot, G P; Kettman, J R (1994) Transplantable polyomavirus-induced salivary gland epitheliomas are populated by immature T cells derived from the host. Cell Immunol 154:1-13
Tuaillon, N; Miller, A B; Longberg, N et al. (1994) Biased utilization of DHQ52 and JH4 gene segments in a human Ig transgenic minilocus is independent of antigenic selection. J Immunol 152:2912-20
Victor, K D; Capra, J D (1994) An apparently common mechanism of generating antibody diversity: length variation of the VL-JL junction. Mol Immunol 31:39-46
Pascual, V; Verkruyse, L; Casey, M L et al. (1993) Analysis of Ig H chain gene segment utilization in human fetal liver. Revisiting the ""proximal utilization hypothesis"". J Immunol 151:4164-72
Tuaillon, N; Taylor, L D; Lonberg, N et al. (1993) Human immunoglobulin heavy-chain minilocus recombination in transgenic mice: gene-segment use in mu and gamma transcripts. Proc Natl Acad Sci U S A 90:3720-4
Huang, Y W; Richardson, J A; Tong, A W et al. (1993) Disseminated growth of a human multiple myeloma cell line in mice with severe combined immunodeficiency disease. Cancer Res 53:1392-6
Yin, X M; Vitetta, E S (1992) The lineage relationship between virgin and memory B cells. Int Immunol 4:691-8
Lee, W T; Vitetta, E S (1992) Memory T cells are anergic to the superantigen staphylococcal enterotoxin B. J Exp Med 176:575-9
Berton, M T; Vitetta, E S (1992) IL-4-induced expression of germline gamma 1 transcripts in B cells following cognate interactions with T helper cells. Int Immunol 4:387-96
Yefenof, E; Ela, C; Kotler, M et al. (1992) Induction of IL-4 secretion by the radiation leukemia virus (RadLV): role in autocrine growth stimulation of RadLV infected pre-leukemic cells. Int J Cancer 50:481-5

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