TUBERCULOSIS IN HIV-POSITIVE PATIENTS - CELLULAR-RESPONSE AND IMMUNE ACTIVATION IN THE LUNG

The host response to Mycobacterium tuberculosis is dependent on the ac cumulation and activation of cytotoxic and memory CD4(+) T cells, resu lting in granuloma formation and delayed type hypersensitivity. We cha racterized the cellular response of radiographically involved lung seg ments from 17 HIV-positive and 11 HIV-negative patients with acute tub erculosis (TB) using bronchoalveolar lavage (BAL) and compared the res ponse to uninvolved segments, normal control subjects and peripheral b lood. 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 lymph ocytes recovered compared with uninvolved segments or normal control s ubjects, but HIV-positive patients had a lower proportion of lymphocyt es in the involved segments than HIV-negative patients with tuberculos is (19 +/- 5% versus 33 +/- 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentag es of CD4(+) lymphocytes (CD4(+) lymphocytes in HIV-positive TB involv ed 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-negat ive patients showed similar lymphocyte subset profiles as BAL, indicat ing that BAL reflects cell populations in tissue granulomas. BAL lymph ocytes from four HIV-positive and four HIV-negative tuberculosis patie nts demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apopt osis (HIV positive 48 +/- 6%, HIV negative 31 +/- 7%, normals 11 +/- 5 %). Steady state mRNA for gamma-interferon was decreased in four HIV-p ositive patients when compared with four HIV-negative patients. IL-8 p roduction was comparable in HIV-negative and HIV-positive patients wit h focal disease but reduced in two patients with miliary tuberculosis. We conclude that HIV-positive patients with tuberculosis have a reduc ed enrichment and activation of immune cells in the lung, and this fai lure of a CD4(+) alveolitis limits an effective immune response.