Phenotypical and Functional Analysis of Bronchoalveolar Lavage Lymphocytes in Patients with HIV Infection

Abstract

The lungs of patients with acquired immunodeficiency syndrome (AIDS) are frequently affected by opportunistic and nonopportunistic infections and pulmonary localizations of Kaposi's sarcoma. The aim of this study was to verify whether, in patients with human immunodeficiency virus (HIV) infections, immunologic pulmonary abnormalities set the stage for the lung complications. For this purpose, a phenotypic and functional characterization of lymphocytes recovered from the bronchoalveolar lavage (BAL) fluid of 24 patients with clinical symptoms and signs of HIV infections was performed (six patients with constitutional disease, five patients with neurologic manifestations, and 13 patients with full-blown AIDS). Our data showed that (1) in patients with HIV, the percentage and absolute number of pulmonary CD8 cells were significantly increased over those in control subjects (in 25% of these patients, mostly with full-blown AIDS, CD8 cells sustained an alveolitis); (2) lung CD4 cells were reduced in percentage but not in absolute number, with the exception of patients with AIDS in whom a significant decrease of the absolute number of BAL CD4 cells has been found (further phenotypic analysis of CD4 lymphocytes showed a reduction of the expression of T4A, B, and E with respect to the T4, T4C, T4D, and T4F epitopes); (3) although the number of BAL cells bearing NK-related determinants was increased, we were unable to demonstrate any in vitro natural killer cell activity. We suggest that the impairment of a proper NK activity in the lungs of these patients might be central to the mechanisms leading to the in situ immunodeficiency state and to the pulmonary complications characterizing AIDS.

High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage

“…35 Alternatively, local HIV-specific T-cell responses in BAL may suppress viral replication by direct anti-viral effector mechanisms including cytolysis of infected cells and secretion of antiviral chemokines and cytokines. While early studies of BAL lymphocytes suggested that the presence of cytotoxic HIV-specific CD8 T cells was associated with poor clinical outcome, [38][39][40][41][42] we found functional HIV-specific CD8 T cells in the BAL of all HIVinfected individuals we studied. Indeed, the local presence of polyfunctional HIV-specific T cells and the CCR5-binding chemokines, which they may produce, was associated with an apparent protection against high frequencies of HIV infection and massive depletion of mucosal CD4 T cells.…”

Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy

“…In HIV-infected subjects, pulmonary infections are common and likely due to the failure of local immunity during the course of disease (14). Additionally, the ability to repeatedly access the lung compartment by BAL permits a relatively noninvasive way to monitor mucosal responses, which has been shown to have prognostic value in early HIV studies (1,28). Lymphocytes obtained from BAL are analogous to lymphocytes obtained from other noninductive mucosal sites, such as the GI lamina propria, as they lack a naïve population (unlike PB).…”

Pulmonary alveolar macrophages from patients with active sarcoidosis express type IV collagenolytic proteinase. An enzymatic mechanism for influx of mononuclear phagocytes at sites of disease activity.

“…Lung T cells were identified by their reactivity with an MAb (OKT3) belonging to the CD3 cluster, whereas T subpopulations were stained with MAbs belonging to the CD8 (OKT8 and Leu 2) and CD4 (OKT4 and Leu 3) clusters, which include suppressor/cytotoxic and helper-related cells, respectively. The frequency of BAL cells positive for the above reagents was determined by flow cytometry, as previously reported elsewhere ( 12).…”