TY - JOUR
T1 - Tuberculosis in HIV-positive patients
T2 - Cellular response and immune activation in the lung
AU - Law, Kevin F.
AU - Jagirdar, Jaishree
AU - Weiden, Michael D.
AU - Bodkin, Marion
AU - Rom, William N.
PY - 1996
Y1 - 1996
N2 - The host response to Mycobacterium tuberculosis is dependent on the accumulation and activation of cytotoxic and memory CD4+ T cells, resulting in granuloma formation and delayed type hypersensitivity. We characterized the cellular response of radiographically involved lung segments from 17 HIV- positive and 11 HIV-negative patients with acute tuberculosis (TB) using bronchoalveolar lavage (BAL) and compared the response to uninvolved segments, normal control subjects and peripheral blood. In both HIV-positive and HIV-negative patients, radiographically involved segments had significantly increased numbers of total cells per milliliter, percent of neutrophils recovered, and percent of lymphocytes recovered compared with uninvolved segments or normal control subjects, but HIV-positive patients had a lower proportion of lymphocytes in the involved segments than HIV-negative patients with tuberculosis (19 ± 5% versus 33 ± 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentages of CD4+ lymphocytes (CD4+ lymphocytes in HIV-positive TB involved site 25 ± 6%; HIV-negative TB involved site 73 ± 2%; p < 0.01) and an increase in the percentage of CD8+ lymphocytes (HIV positive involved site 61 ± 6% versus HIV negative involved site 19 ± 3%; p < 0.01). Immunohistochemistry of lung biopsy tissue in five HIV-negative patients showed similar lymphocyte subset profiles as BAL, indicating that BAL reflects cell populations in tissue granulomas. BAL lymphocytes from four HIV-positive and four HIV-negative tuberculosis patients demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apoptosis (HIV positive 48 ± 6%, HIV negative 31 ± 7%, normals 11 ± 5%). Steady state mRNA for γ-interferon was decreased in four HIV-positive patients when compared with four HIV-negative patients. IL-8 production was comparable in HIV-negative and HIV-positive patients with focal disease but reduced in two patients with miliary tuberculosis. We conclude that HIV-positive patients with tuberculosis have a reduced enrichment and activation of immune cells in the lung, and this failure of a CD4+ alveolitis limits an effective immune response.
AB - The host response to Mycobacterium tuberculosis is dependent on the accumulation and activation of cytotoxic and memory CD4+ T cells, resulting in granuloma formation and delayed type hypersensitivity. We characterized the cellular response of radiographically involved lung segments from 17 HIV- positive and 11 HIV-negative patients with acute tuberculosis (TB) using bronchoalveolar lavage (BAL) and compared the response to uninvolved segments, normal control subjects and peripheral blood. In both HIV-positive and HIV-negative patients, radiographically involved segments had significantly increased numbers of total cells per milliliter, percent of neutrophils recovered, and percent of lymphocytes recovered compared with uninvolved segments or normal control subjects, but HIV-positive patients had a lower proportion of lymphocytes in the involved segments than HIV-negative patients with tuberculosis (19 ± 5% versus 33 ± 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentages of CD4+ lymphocytes (CD4+ lymphocytes in HIV-positive TB involved site 25 ± 6%; HIV-negative TB involved site 73 ± 2%; p < 0.01) and an increase in the percentage of CD8+ lymphocytes (HIV positive involved site 61 ± 6% versus HIV negative involved site 19 ± 3%; p < 0.01). Immunohistochemistry of lung biopsy tissue in five HIV-negative patients showed similar lymphocyte subset profiles as BAL, indicating that BAL reflects cell populations in tissue granulomas. BAL lymphocytes from four HIV-positive and four HIV-negative tuberculosis patients demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apoptosis (HIV positive 48 ± 6%, HIV negative 31 ± 7%, normals 11 ± 5%). Steady state mRNA for γ-interferon was decreased in four HIV-positive patients when compared with four HIV-negative patients. IL-8 production was comparable in HIV-negative and HIV-positive patients with focal disease but reduced in two patients with miliary tuberculosis. We conclude that HIV-positive patients with tuberculosis have a reduced enrichment and activation of immune cells in the lung, and this failure of a CD4+ alveolitis limits an effective immune response.
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U2 - 10.1164/ajrccm.153.4.8616569
DO - 10.1164/ajrccm.153.4.8616569
M3 - Article
C2 - 8616569
AN - SCOPUS:0029881009
VL - 153
SP - 1377
EP - 1384
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 4
ER -