This research investigates human lymphocyte cell surface molecules relevant to immune function. The methodology is based on the production of murine monoclonal antibodies recognizing distinct differentiation antigens. With these reagents, it is possible to identify both immature T cells and mature functionally distinct T-cell subsets. Selected antibodies can also be used as probes to study the function and potential receptor role of specific T-cell surface molecules. By generating panels of antibodies capable of recognizing different epitopes on functionally significant molecules, it will be possible to explore the relationship between structure and function. Selected antibodies will also be used for the isolation and purification of specific molecules for biochemical characterization and amino acid sequencing. Experiments are directed towards identifying differentiation markers for suppressor cell subsets as well as for surface molecules that may be uniquely related to suppressor cell function. Clinically, these studies are relevant to the further understanding of the pathogenesis of immune deficiency disorders such as those occurring in the acquired immunodeficiency syndrome (AIDS), certain patients with malignancy, hemophiliacs, and in patients following bone marrow transplantation. Immune reconstitution and complications related to immunodeficiency constitute major issues in clinical marrow transplantation. We will address these questions by evaluating the kinetics of lymphoid reconstitution and by characterizing the functional capacity of cells appearing during the post-transplant period, especially immature lymphoid cells. The identification of immature lymphocytes, or precursor T cells, will provide the opportunity to study the potential effects of lymphokines and thymic hormones and on thymic epithelial cell monolayers as means for induction of differentiation and maturation. This could have general relevance to further understanding and treatment of multiple immune deficiency disorders. (CS)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029548-06
Application #
3168752
Study Section
Immunobiology Study Section (IMB)
Project Start
1980-08-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Pacific Northwest Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98122
Moretti, L; Corpuz, S; Giuliodori, L et al. (1991) Quantitation of T cell depletion by limiting dilution analysis. Haematologica 76:188-92
Egeland, T; Albrechtsen, D; Martin, P J et al. (1990) Immunomagnetic depletion of CD6+ cells from bone marrow and peripheral blood. Bone Marrow Transplant 5:193-8
Jung, L K; Haynes, B F; Nakamura, S et al. (1990) Expression of early activation antigen (CD69) during human thymic development. Clin Exp Immunol 81:466-74
Voltarelli, J C; Przepiorka, D; Shankar, P et al. (1989) CD8+/DR+/CD25--T-lymphocytes associated with marrow graft failure. Bone Marrow Transplant 4:647-52
Bjorndahl, J M; Sung, S S; Hansen, J A et al. (1989) Human T cell activation: differential response to anti-CD28 as compared to anti-CD3 monoclonal antibodies. Eur J Immunol 19:881-7
Morishita, Y; Sao, H; Hansen, J A et al. (1989) A distinct subset of human CD4+ cells with a limited alloreactive T cell receptor repertoire. J Immunol 143:2783-9
Martin, P J; Hansen, J A; Anasetti, C et al. (1988) Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies. Am J Kidney Dis 11:149-52
Bjorndahl, J M; Nakamura, S; Hara, T et al. (1988) The 28-kDa/32-kDa activation antigen EA 1. Further characterization and signal requirements for its expression. J Immunol 141:4094-100
Martin, P J; Hansen, J A; Torok-Storb, B et al. (1988) Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease. Bone Marrow Transplant 3:437-44
Martin, P J; Clift, R A; Fisher, L D et al. (1988) HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: analysis of survival and remission duration. Blood 72:1978-84

Showing the most recent 10 out of 31 publications