Background: A positive Interferon-γ release assay (IGRA+) after exposure to tuberculosis indicates a systemic immune response to Mycobacterium tuberculosis (MTB). However, most people will remain IGRA-negative (IGRA-) after exposure. In mice, regulatory T-lymphocytes (T reg ) can deter the pulmonary clearance in early infection, possibly preventing a systemic immune response. Objective: To study the local immunity in TB-exposed health care workers without active disease. Methods: FACS analysis on bronchoalveolar lavage (BAL) cells including T reg cells (CD4+CD25+CD127-) and activated macrophages (HLA-DR+). Questionnaire for demographic, and health-related data. Blood IGRA. Results: Demographic and epidemiological parameters were not statistically different. Of 10 IGRA- and 12 IGRA+ subjects, the BAL of the latter group showed a higher frequency of T reg cells (median 2,5% range 1.4-4.4% vs. 0.7% 0.2-1.3%; p=0.0001 for Mann-Whitney test). In contrast, the frequency of T reg cells in among peripheral blood monocytes (PBMC) was similar in both groups (22% 10-38% vs. 21% 9-27%; p=0.87). Accordingly, activated macrophages in the BAL were found more frequently in IGRA-positive than in IGRA negative subjects (median 89% range 77-100 vs. 95% 85-100; p=0.04), while there was no difference in blood (91% 82-94% vs. 86% 74-96%; p=0.34). Conclusion: In healthy contacts of tuberculosis patients, a positive IGRA response is associated with expansion of T reg cells and activated macrophages in the BAL but not in peripheral blood. The role of these cell populations for the prevention of systemic immune responses to MTB needs to be further evaluated.
Herzmann et al. (Thu,) studied this question.