TY - JOUR
T1 - Enhanced responses to mycobacterium tuberculosis antigens by human alveolar lymphocytes during active pulmonary tuberculosis
AU - Schwander, Stephan K.
AU - Torres, Martha
AU - Sada, Eduardo
AU - Carranza, Claudia
AU - Ramos, Esther
AU - Tary-Lehmann, Magdalena
AU - Wallis, Robert S.
AU - Sierra, Juan
AU - Rich, Elizabeth A.
N1 - Funding Information:
DNA synthesis. PBMC, BAC, or responder T cells (accessory cell–dependent T cells), were added to round-bottom 96-well plates (Nunc, Copenhagen) at 5 × 104 cells/well. For accessory assays, MN or AM were added to accessory cell–dependent T cells in various numbers in triplicate to achieve 5%–100% of the number of responder T cells. Stimuli used were as follows: PPD (Statens Seruminstitut, Copenhagen), 10 mg/mL; Candida albicans (Greer Laboratories, Lenoir, NC), 10 mg/mL; tetanus toxoid (TT; Lederle, Pearl River, NY), 0.7 Lf/mL; staphylococcal enterotoxin B (SEB; Sigma), 5 mg/mL; phytohemagglutinin (PHA; Sigma), 1 mg/mL; mannose-capped lipoarabinomannan (manLAM, purified from M. tuberculosis strain H37Rv culture filtrate; endotoxin contamination, 3.46 ng/1.0 mg of manLAM, determined by limulus amoebocyte assay), 10 mg/mL; and 30/32-kDa antigen 85–protein complex (Ag 85 A, B, and C from M. tuberculosis H37Rv culture filtrate, which is referred to as Ag 85), 5 mg/mL [28]. ManLAM and Ag 85 were kindly provided by J. T. Belisle (Colorado State University, Department of Microbiology, Fort Collins, funded through NIH contract AI-25147). Concentrations of stimuli used and periods of culture were those resulting in peak responses by PBMC as determined in preliminary experiments. Cells were pulsed with 1 mCi/well [3H]thymidine (Amersham, Amersham, UK; specific activity, 5 Ci/mmol) on day 2 (PHA), day 3 (SEB), and day 4 (manLAM, Ag 85, TT, Candida antigen, and PPD). Cells were harvested at ∼24 h after addition of [3H]thymidine. Incorporation of [3H]thymidine was determined with a scintillation counter and expressed as counts per minute.
PY - 1998/1/1
Y1 - 1998/1/1
N2 - 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 / 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 Thl-type cytokine host response.
AB - 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 / 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 Thl-type cytokine host response.
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U2 - 10.1086/314454
DO - 10.1086/314454
M3 - Article
C2 - 9780265
AN - SCOPUS:0031724656
SN - 0022-1899
VL - 178
SP - 1434
EP - 1445
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -