Dept. of Microbiology, Immunology & Molecular Genetics
UCLA School of Medicine
Los Angeles, CA 90095
Dept. Microbiology, Immunology & Molecular Genetics
UCLA School of Medicine
Los Angeles, CA 90095
Office
BSRB 190C
Los Angeles, CA 90095
Laboratory
BSRB 173
Los Angeles, CA 90095
Human T Cell Development Studies of human T cell development are the major focus of the laboratory. These studies are being pursued in in vitro thymocyte suspension cultures, thymic organ culture and in vivo in the SCID/hu mouse. We are interested in examining the role of cytokines on normal thymocyte maturation. We want to assess whether cytokine administration can augment stem cell reconstitution strategies in diseases such as infection with the human immunodeficiency virus (HIV) and malignancies. In addition, understanding the interaction between HIV and the developing T cell in the thymus is an important focus of the laboratory. Our studies are intended to test the hypotheses that: 1). thymocyte subsets which are activated and/or proliferating are the principle targets for HIV infection; 2). cytopathic viral strains affect thymocytes at an earlier stage of maturation than non-cytopathic strains and 3). depletion of thymocytes which produce IFN-g results in increased HIV expression by thymocytes and contributes to immunodeficiency. Studies of human T cell development are the major focus of the laboratory. These studies are being pursued are in vitro thymocyte suspension cultures, thymic organ cultures and in vivo in the SCID/hu mouse. We are interested in examining the role of cytokines on normal thymocyte maturation. We want to assess whether cytokine administration can augment stem cell reconstitution strategies in disease such as infection with the human immunodeficiency virus (HIV) and malignancies. In addition, understanding the interaction between HIV and the developing T cell in the thymus is an important focus of the laboratory. Our studies are intended to test the hypothesis that: 1) thymocyte subsets which are activated and/or proliferating are the targets for HIV infection; 2) cytopathic viral strains affect thymocytes at an earlier stage of maturation than non-cytopathic strains and 3) depletion of thymocytes which produce IFN-. results in increased HIV expression by thymocytes and contribution to immunodeficiency. Besides studying the effects of HIV on the developing immune system, we are continuing our research to determine how cytokines affect cell growth and the phenotype of malignant immature T cell leukemias. We have shown that there is a correlation between stage of maturation of the T cell leukemias and expression of the transcription factor c-jun which binds to the AP-1 binding site. Therefore, we want to delineate the role of the nuclear factors in normal and malignant T cell growth and differentiation. Understanding the normal developing immune system and its deregulation in HIV disease and leukemias may provide new avenues for medical intervention.
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