Humoral regulation of the immune spectrum in a guinea pig model of tuberculosis

Abstract

The inverse relationship between antibody titers and effective T cell function in tuberculosis at the extremes of the disease spectrum is intriguing. The purpose of this study is to determine if humoral immunity regulates cell mediated immunity in an experimental model of pulmonary tuberculosis. Immune complexes containing mycobacterial antigens could bind T cells with Fc receptors for IgG (T[gamma]) and alter their activity. Immunodominant antigens for B cells in the guinea pig were determined by western blot using three protein fractions (culture filtrate, cell wall/membrane, and cytoplasm) of virulent Mycobacterium tuberculosis H37Rv. The guinea pigs were immunized with BCG and/or aerogenically infected with M. tuberculosis H37Rv. Some animals were fed a low protein diet to mimic anergic human tuberculosis. Individual guinea pigs exhibited considerable variability in their antibody responses. Well nourished animals responded well to the 55, 27, 25, 19, and 10 kDa proteins of the culture filtrate and the 19, 14, and 8 kDa proteins of the cell wall. Malnourished guinea pigs responded uniformly to the cell wall proteins of 29 and 25 kDa. None of the immunized or infected animals had detectable antibody against cytoplasmic proteins. Immune complexes in guinea pig plasma were isolated by polyethylene glycol precipitation. Malnourished guinea pigs had levels of immunoglobulin in complexes of 2.05 μg/ml and well nourished animals had 2.145 μg/ml, as determined by an enzyme immunoassay. Antibody titers of malnourished guinea pigs to culture filtrate proteins were 16 to 32 compared to 8 to 16 in well nourished animals. The presence of whole immune plasma suppressed the Con A- and PPD-induced proliferation only in cultures containing T[gamma] cells. The removal of immune complexes from plasma abrogated the suppression of the T[gamma] cells by whole plasma. The cells from malnourished guinea pigs were unaffected by the presence or absence of T[gamma] cells or whole immune plasma. We have identified a mechanism by which immune complexes in whole plasma suppresses the mitogen- and antigen-induced proliferation of T[gamma] cells in vitro. In malnourished guinea pigs, lymphoproliferation is apparently suppressed by an entirely different mechanism, not involving immune complexes and T[gamma] cells.