Comparative and Prospective Study of Different Immune Parameters in Healthy Subjects at Risk for Tuberculosis and in Tuberculosis Patients

Abstract

It has not been fully elucidated which of the components of the immune response against Mycobacterium tuberculosis is indicative of resistance or susceptibility. The aim of this study was to identify an immune parameter that could be indicative of either resistance or susceptibility to M. tuberculosis infection. We prospectively studied (three determinations, at months 0, 8, and 12) 15 patients with chronic pulmonary tuberculosis and 42 healthy individuals with a recent and frequent contact with tuberculosis patients. Peripheral blood mononuclear cells were stimulated with a whole-protein extract or the 30-kDa antigen of M. tuberculosis for 6 days, and several immune parameters were determined. No consistent differences between tuberculosis patients and healthy controls were detected in most immune parameters studied, including the expression of different activation antigens, cytokine secretion, lymphocyte proliferation, and nitric oxide production. However, the synthesis of tumor necrosis factor alpha, the intracellular detection of gamma interferon, and the apoptosis of monocytes under certain culture conditions tended to show clear-cut differences in cells from patients and controls (P < 0.05 in all cases for most determinations). Nevertheless, when results were analyzed on an individual basis, it was evident that a significant degree of overlapping of values from patients and controls occurred for all parameters studied. We conclude that although the immune parameters tested do not allow the identification of individuals susceptible to M. tuberculosis, the specificity and sensitivity of some of them could be improved through future studies.

CD69 Expression on CD4+T Lymphocytes after In Vitro Stimulation with Tuberculin Is an Indicator of Immune Sensitization againstMycobacterium tuberculosisAntigens

“…The mean values for the expression of CD69 in groups of patients with clinically inactive TB and healthy individuals with a positive TST reaction were, however, lower. The highest levels of IFN-␥ in our study, as well as in previous (8,26,32,37,38), were observed in the group of healthy individuals with a positive TST reaction and patients with clinically inactive TB. The mean levels of IFN-␥ secreted by the group of patients with culture-proven active TB before treatment were lower.…”

“…The expression of the early lymphocyte activation marker CD69 after stimulation with tuberculin has been evaluated in healthy individuals with positive and negative TST results and has been shown to correlate well with the TST induration diameter (30). A significantly higher level of expression of CD69 was found in patients with TB 8 months after they started treatment compared to that in healthy controls (26). Furthermore, in patients coinfected with HIV type 1 and M. tuberculosis, the expression of CD69 correlated with the results of TST and IFN-␥ production in PPD-stimulated CD4 T lymphocytes (15).…”

Evaluation of memory immune response to mycobacterium extract among household contact of tuberculosis cases

“…In this study, there was also no significant difference in the secretion of IL-10 by PBMCs from household contacts with or without a history of TB. Similarly, another study showed that patients with chronic TB and healthy communicants presented IL-10 levels that did not allow discrimination between individuals with susceptibility or resistance to TB (21). This finding suggested that T memory cells circulated and responded in the same way in individuals who had been exposed to the same source of mycobacterium, independent of their susceptibility toward developing TB.…”

Selected Pool of Peptides from ESAT-6 and CFP-10 Proteins for Detection of Mycobacterium tuberculosis Infection

“…The TST is widely used for the diagnosis of M. tuberculosis infection but has several drawbacks such as cross-reactivity, poor specificity, limited sensitivity, and the need for a followup visit limits its reliability (10,12,20,21). In the past few years, in vitro tests of cell-mediated immunity, in particular LPA and IFN-␥ detection in the supernatant of stimulated cultures, have been used for diagnosing TB (12,13,32,33). However, these assays exhibited a low specificity due to the cross-reactivity of the Ags used (whole protein extracts or the 30-kDa Ag of M. tuberculosis, BCG, and PPD).…”