High Proportion of Gamma-Delta T Cell Receptor Positive T Cells in Bronchoalveolar Lavage and Peripheral Blood of HIV-lnfected Patients with <i>Pneumocystis carinii</i> Pneumonias

Abstract

To investigate the local immunological situation in the lung of HIV-infected patients with Pneumocystis carinii pneumonias (HIV-PCP), we analyzed the proportion and the distribution of lymphocyte subpopulations and their state of activation in bronchoalveolar lavage (BAL) and peripheral blood of 21 HIV-PCP patients (CDC classification group IV) compared to 24 HIV-negative patients with interstitial lung diseases (ILD). Peripheral blood lymphocytes (PBL) and BAL cells were stained with monoclonal antibodies. Two-color cytofluorometric analysis (flow cytometry) was performed with a cytofluorograph (Epics Profile, Coulter Corp., Hialeah, Fla., USA). In BAL from HIV-PCP patients the number of CD3-positive lymphocytes was significantly increased, yet there was no difference in the number of macrophages and neutrophils when compared to patients with ILD. Quantification of lymphocyte sub-populations showed that the increased number of BAL CD3-positive lymphocytes in HIV-PCP patients was mainly due to a significantly increased number of CD8-positive T cells, while the pulmonary CD4-positive T cells were decreased both in relative and absolute numbers. As a consequence, an inverted pulmonary CD4/CD8 ratio resulted for HIV-infected patients with PCP. Analysis of in-vivo-activated T cells in BAL and peripheral blood when measured by the expression of IL-2R, HLA-DR and VLA-1 revealed increased numbers of IL-2R and HLA-DR bearing CD8-positive T cells but significantly decreased numbers of IL-2R and HLA-DR bearing CD4-positive T cells as well as a higher number of CD8/CD57 double positive T cells in HIV-infected individuals when compared to patients with ILD. Moreover, a significantly higher proportion of gamma delta T cell receptor positive T cells (TCR-γ>δ-positive T cells) was found both in BAL and peripheral blood of HIV-infected patients with PCP (p < 0.05 resp. p < 0.001). Our study extends knowledge about the distribution of lymphocyte subsets and their state of activation in HIV-PCP patients when compared to patients with ILD and supports the view that TCR-γ>δ-positive T cells may play an important role in the pulmonary immune defense of HIV-infected patients.

Immunophenotyping of Bronchoalveolar Lavage Lymphocytes

“…Diseases and conditions for which the immunophenotyping of BAL fluid lymphocytes has been investigated include sarcoidosis (8,9,25,27,32,33,43,44,52,55,63,71,75,87,102,120); hypersensitivity pneumonitis (6,17,27,87); asthma (21,38,40,50,56,61,69,79,83,92,96,99,107,109,110,119); infectious diseases including human immunodeficiency virus (2,45,57,85,111,123), tuberculosis (3,49,97,121), human T-cell lymphotropic virus type I infection (74,101), and hepatitis C virus infection (62); lung transplantion…”

Colonization by Pneumocystis jirovecii and Its Role in Disease

“…The role of gamma-delta (␥␦) T cells in Pneumocystis infection has not been as extensively examined; however, studies suggest that they may play a role in controlling inflammation and pulmonary injury associated with infection and possibly a protective role in the context of diminished alpha-beta T cells. In clinical studies, ␥␦ T cells were increased in blood and BAL fluid specimens from HIV-infected individuals with PCP (3,136). In murine models of Pneumocystis infection, early studies suggested that ␥␦ T cell-deficient mice were not susceptible to progressive Pneumocys-tis infection, while other studies indicated that these cells may play a role in control of infection in alpha-beta T cell-deficient models (3).…”

Increased Host Resistance againstPneumocystis cariniiPneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+T Cells

“…Clinical observations have shown that ␥␦-TCR ϩ T cells are elevated in blood and bronchoalveolar lavage (BAL) fluid of individuals with AIDS and P. carinii pneumonia (1,13), although the functional aspects of ␥␦-TCR ϩ T cells in these studies were not studied. Data from prior experimental studies have shown that ␥␦-TCR ϩ T-cell-deficient mice are not permissive for longterm P. carinii infection (10), while another study suggests that ␥␦-TCR ϩ T cells provide residual host defense functions in ␣␤-TCR ϩ T-cell-deficient mice (9).…”