Dietary protein deficiency and Mycobacterium bovis BCG affect interleukin-2 activity in experimental pulmonary tuberculosis

Abstract

Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated. They were maintained for 6 weeks on defined, isocaloric diets containing either 30% (control animals) or 10% (animals receiving low protein) ovalbumin as the sole protein source. Animals were challenged by the respiratory route with a low dose of virulent M. tuberculosis H37Rv and killed 4 weeks later. Proteinmalnourished animals were not protected by previous vaccination with BCG. Lymphocytes isolated from various tissues were tested in vitro for proliferative responses to mitogen (concanavalin A) and antigen (purified protein derivative [PPD]), production of interleukin-2 (IL-2), and response to exogenous recombinant IL-2 (rIL-2). Protein-malnourished guinea pigs responded only weakly to PPD skin tests, and their blood and lymph node lymphocytes exhibited impaired proliferation when cultured with PPD in vitro. IL-2 levels were consistently low in cultures of stimulated blood and spleen lymphocytes from protein-deprived animals. BCG vaccination of nutritionally normal guinea pigs, on the other hand, induced significantly more IL-2 production by PPDand concanavalin A-stimulated lymphocytes. The addition of exogenous mouse rIL-2 (40 and 80 U/ml) in vitro to PPD-stimulated blood and lymph node cells from nonvaccinated, protein-deprived guinea pigs resulted in no improvement of the proliferative response. Previous vaccination of malnourished guinea pigs did not consistently enhance the response of PPD-stimulated lymphocytes to added rIL-2. Dietary protein deficiency and BCG vaccination appear to modulate antigen-driven cellular immunity in animals with tuberculosis by altering the production of, and the response to, IL-2 by PPD-stimulated lymphocytes.

Protein Deficiency Induces Alterations in the Distribution of T-Cell Subsets in Experimental Pulmonary Tuberculosis

“…Although our study did not directly demonstrate enhanced trafficking of lymphocytes from the circulation to the lymph nodes, it is quite likely that the pooling of antigenreactive T lymphocytes in the lymph nodes of protein-deprived guinea pigs occurred at the expense of the circulating population. This may explain, in part, the reduced ability of peripheral lymphocytes to mediate a PPD-induced dermal hypersensitivity reaction in those animals and the impairment of PPDdriven proliferation (Table 2) and IL-2 production observed previously under identical experimental conditions in peripheral lymphocytes (13).…”

“…It is clear from studies of T lymphocytes in vitro that protein deprivation results in intrinsic alterations in function on a per cell basis in guinea pigs infected with M. tuberculosis (4,9,13). Therefore, the putative sequestration of T cells in lymph nodes draining the lung, as suggested in the present study, must be placed in the broader context of the overall impact of dietary protein deficiency on resistance to pulmonary tuberculosis in the guinea pig model (9).…”

“…deficient guinea pigs (LP, 6.1 Ϯ 3.6 mm; C, 15.2 Ϯ 4.8 mm [P Ͻ 0.05]) despite both gross pathologic and bacteriologic evidence of extensive tuberculosis in the lungs, spleen, and bronchotracheal lymph nodes of the LP animals (data not shown). Although we did not perform a comprehensive set of bacteriological studies in these experiments, we have published extensively on the bacterial loads in the tissues of LP and C guinea pigs under identical circumstances, i.e., after 4 weeks of virulent infection (4,(11)(12)(13). Protein-deficient guinea pigs routinely have five-to eightfold-more bacilli in their lungs, spleens, and lymph nodes than do their well-nourished counterparts.…”

“…In previous work with this model of pulmonary tuberculosis, we have observed significant impairment of tuberculin-induced delayed-type hypersensitivity and of proliferation and interleukin-2 (IL-2) production by peripheral blood lymphocytes in protein-deficient animals (9,11,13). At the same time, the bronchotracheal lymph nodes draining the initial site of im-plantation of M. tuberculosis were found in low-protein guinea pigs to contain significantly increased proportions of rosetteforming (CD2-positive) T cells (2) and reduced levels of lymphocytes expressing the Fc receptor for immunoglobulin M (IgM) (FcR ϩ ) (10).…”

Genetic and management factors that influence the susceptibility of cattle toMycobacterium bovisinfection

“…In a study in Mexico, cattle that were infected with M. bovis were reported to be mostly in fair to good body condition (Milian-Suazo et al, 2000). However, since protein deficiency has been shown to reduce immunocompetence in guinea-pigs (McMurray et al, 1989), it is possible that there are nutritional effects in cattle that have not been elucidated. Experience from collective farms in Czechoslovakia suggests that deficiencies in vitamins A and C, calcium and protein, as well as carbohydrate excess, are likely to increase the risk of cattle acquiring M. bovis infection (Kabrt, 1962).…”