IMMUNOSUPPRESSION AND ALTERATION OF RESISTANCE TO PULMONARY TUBERCULOSIS IN GUINEA-PIGS BY PROTEIN UNDERNUTRITION

The impact of chronic moderate protein deficiency on resistance to pulmonary tuberculosis was studied in a guinea pig model. Inbred and outbred guinea pigs were maintained on isocaloric diets containing 30% or 10% ovalbumin, vaccinated with Mycobacterium bovis BCG vaccine and infected by the respiratory route with virulent Mycobacterium tuberculosis. Protein deficiency was associated with significant loss of dermal tuberculin hypersensitivity, reduced purified protein derivative (PPD)-driven lymphoproliferation in vitro and diminished interleukin-2 production. The proportion of E rosette receptor (CD2) positive lymphocytes was significantly lower in the blood and thymus of low-protein guinea pigs. Increased levels of circulating anti-PPD antibodies were associated with loss of delayed hypersensitivity in protein-deprived animals. Immune complexes containing these antibodies may act on T cells bearing Fc receptors for immunoglobulin G (T-gamma cells), which appear to exert a suppressive effect on antigen-induced lymphoproliferation of T(non-gamma) cells in vitro. These results imply an important immunoregulatory role for T-gamma cells in tuberculosis and suggest one mechanism whereby resistance to tuberculosis is altered in protein malnutrition.