Enhanced Responses toMycobacterium tuberculosisAntigens by Human Alveolar Lymphocytes during Active Pulmonary Tuberculosis

Abstract

Responses to mycobacterial and nonmycobacterial antigens were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from patients with active pulmonary tuberculosis (n=16) and healthy subjects (n=23). DNA synthesis in BAC (but not PBMC) from tuberculosis patients was significantly increased in response to the mycobacterial antigens purified protein derivative (PPD), antigen 85, and mannose-capped lipoarabinomannan but not to nonmycobacterial antigens. The response to PPD was also increased in enriched alveolar lymphocytes from tuberculosis patients (P<.05). The frequency of interferon-gamma but not interleukin-4- or -10-producing cells by ELISAspot was increased in PPD-stimulated BAC from patients with tuberculosis (P<.05). Accessory function of alveolar macrophages for T lymphocyte responses was similar and suppressive activity was variably decreased in tuberculosis patients. Thus, there is compartmentalization of mycobacterial antigen-specific lymphocytes to the lungs during active tuberculosis that on challenge produce a Th1-type cytokine host response.

Pulmonary Mononuclear Cell Responses to Antigens ofMycobacterium tuberculosisin Healthy Household Contacts of Patients with Active Tuberculosis and Healthy Controls from the Community

“…Proportions of alveolar neutrophils were Յ1% in BAC of both HHC and CC. Median proportions of alveolar lymphocytes were 14.1 and 14.0% and of alveolar macrophages were 85.8 and 83.9%, in HHC and CC, respectively, similar to those in CC in previous studies (10,26).…”

“…A nonmycobacterial Ag prepared from Candida albicans (Candida; Greer Laboratories, Lenoir, NC) was used to assess the specificity of responses. All Ags were used in concentrations that resulted in peak stimulation, as determined in previous studies (10). Dose responses were determined for Ag 85A, Ag 85B, Ag 85C, ESAT-6, and ST-CF for optimal induction of DNA synthesis, and performance of IFN-␥ and IL-10 enzymelinked immunospot (ELISPOT) assays.…”

“…In patients with pulmonary tuberculosis, however, M. tuberculosis Ag-specific IFN-␥-producing cells (10) and spontaneous IFN-␥ production (11) are compartmentalized to the site of infection (the lung) despite ongoing disease. Tuberculosis patients represent subjects who are at one end of the spectrum of M. tuberculosis infection, i.e., individuals who have lost immunological control, reactivated their infectious focus, and developed disease.…”

Mycobacterium tuberculosis strains from ancient and modern lineages induce distinct patterns of immune responses

“…However, this relation was not always apparent in experimental conditions. Some investigators reported up regulation of this cytokine [22,25] and some showed the reverse [26,27]. In our earlier study with THP-1, we found a strain specific induction of IL-10.…”

Mast Cell Activation byMycobacterium tuberculosis: Mediator Release and Role of CD48

“…Following penetration of the mucosal barrier, the bacteria are associated with intraepithelial leukocytes and subsequently conveyed to the draining lymph nodes (3). From human and animal models of tuberculosis infection, the primary effector cells implicated to date in the control of tuberculosis have been T lymphocytes and alveolar and interstitial macrophages (4). However, other cell types, such as dendritic cells (5), type II pneumocytes (6), endothelial cells, and fibroblasts (7), have been reported to phagocyte M. tuberculosis, suggesting that many other cell types may be involved in the immunological control of M. tuberculosis in the lung.…”