There is a striking contrast between the obvious importance of tuberculosis as a major cause of morbidity and mortality worldwide, including its re-emergence in this country as an opportunist in AIDS patients, and the paucity of detailed knowledge about the pathogenesis and relevant immune responses of this disease. The ultimate objective of this research is to elucidate the role of immunoregulatory T lymphocytes, specifically subsets of T-cells bearing receptors for the Fc portion of immunoglobulin (FcR+), in resistance to pulmonary tuberculosis. The importance of FcR+ cells in the host-parasite relationship in tuberculosis is strongly supported by clinical studies. The functions of FcR+ T-cells will be studied in a highly relevant, quantitatively precise and easily manipulated model of respiratory tuberculosis in inbred guinea pigs. Both functional (rosette) assays and monoclonal antibodies specific for IgG Fc (Fc R) are available for enumeration and separation of T cells from blood, lymphoid organs, primary tubercles and tuberculin skin reaction sites of BCG-vaccinated and non-vaccinated inbred Strain 2 guinea pigs following respiratory challenge with 3-5 virulent Mycobacterium tuberculosis. The antigenic reactivity of T-gamma subsets will be defined in vitro in a proliferation assay with purified mycobacterial antigens and synthetic peptides. The role of MHC class II antigens in mycobacterial antigen presentation to T cells will be assessed using presenting cells from Strain 13 guinea pigs. The influence of BCG vaccination and/or virulent pulmonary challenge on the ability of T-gamma cells to produce functional interluekin 2 (IL2) and express IL2 receptors in response to antigen in vitro will be studied. The inducer and suppressor functions of T cells will be examined both in vitro (co-culture studies) and in vivo (passive transfer studies). The influence of anti-mycobacterial antibodies and immune complexes containing IgG on the functions of T-gamma cells will be determined both in vitro and in vivo.
