This work is an investigation of aspects of cell mediated immunity (CMI) in resistance to infection with Chlamydia trachomatis. Chlamydia trachomatis infection and its sequellae (which includes scarring in the eye leading to blinding trachoma and scarring in the upper genital tract leading to infertility) are major health problems throughout the world. Hose defense mechanisms against this infection are poorly understood - and cell mediated immunity in particular may be a double-edged sword leading to both protection and immunologically mediated scarring. This project will investigate the role of CMI in host defense and immunopathology examining production of cytokines and their function during chlamydial pneumonia in a mouse model. Chlamydial antigen has been shown in our model when incubated with immune whole spleen cells (WSC) to lead to production of interferon-gamma (IFN-gamma). Using this system we will test for production of other cytokines as well including IL-1, IL-2 tumor necrosis factors (alpha and beta) and colony stimulating factors. The identity of the cells producing these factors will be determined by panning and antibody - complement depletion studies. The ability of specific cytokines to protect against Chlamydia will be tested in vitro and in vivo by infusion and depletion (by specific antibody) studies. Synergy between cytokines - such as IFN-gamma and TNF will also be examined. The in vivo effect of cytokines on scarring in the lung will also be observed. NK function will be examined by measuring antibody and other immunologic parameters after stimulation or depletion of NK cells. Persistence will be studied by timed in vitro incubation of lung lavage cells at various intervals post infection. Macrophage/cytokine interaction will be studied employing immunodeficient beige and P mice. Other aspects of CMI such as the role of natural killer cells in control of immunology, the role of CMI in persistence of infection, and the in vivo interaction of cytokines and macrophages will also be examined. These studies will help to better define the role of CMI in host defense and immunopathology with Chlamydia trachomatis infection.
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