Lung T cells in hypersensitivity pneumonitis: phenotypic and functional analyses.

Abstract

Cells recovered from bronchoalveolar lavage (BAL) and tissue sections from transbronchial lung biopsies were studied in 16 patients with symptomatic hypersensitivity pneumonitis (HP) and in six subjects with a similar history of exposure but without features of disease by using a series of monoclonal antibodies (MoAb) detecting different lymphocyte subpopulations, including T and T subsets, B lymphocytes, and natural killer (NK) cells. Their functional activities in cytotoxic and suppressor assays and the microenvironment in the lung by using immunohistological techniques were also evaluated. It has been demonstrated that the majority of cells recovered from BAL of HP patients are represented by T8 lymphocytes, with a relevant imbalance of the T4/T8 ratio (p less than 0.001). HNK-1+ cells were markedly increased (p less than 0.001), whereas the frequency of cells bearing other NK-related markers (NK-15, VEP 13, Ab8.28, T10, M1, and Fc gamma R) were not significantly increased with respect to controls. Immunohistological study confirmed that the majority of cells infiltrating lung parenchyma are T8+ lymphocytes. The number of HNK-1+ cells detected on lung biopsies was very low in all cases, even in patients with the highest values on BAL suspensions. The evidence of cells bearing the proliferation-associated markers (Tac and T9 antigens) seems to support the hypothesis of a local proliferation in the lung. In terms of phenotypic analysis, the results observed in the group of asymptomatic individuals are qualitatively superimposable on those observed in the HP group, but the magnitude of the phenomenon is less prominent and therefore the data are not as statistically significant as that produced by the comparison between HP patients and the same controls. Functional analysis of BAL T cells from both HP patients and asymptomatic individuals showed suppressor activity in vitro, as determined by the ability to influence a pokeweed mitogen (PWM)-driven B cell differentiation assay. BAL cells from HP patients were also able to display a definite cytotoxic function in vitro, whereas BAL lymphocytes from asymptomatic subjects did not. Taken together, these data demonstrated that cells responsible for the alveolitis in patients with HP are characterized by the expansion of T cells with the phenotype and functions of both suppressor and/or cytotoxic lymphocytes. This expansion is likely to be related to a local immunologic response to the antigenic stimulus and may provide new insights into the pathogenetic mechanisms of this disease, its pathological pattern, and its management.

Lymphocyte subsets in hypersensitivity pneumonitis

“…The total number of cells recovered by BAL from patients with hypersensitivity pneumonitis is greatly increased, being three to five times that observed from controls Dept of Thoracic Medicine, Guy's Hospita.l, St. Thomas Street, London SEl 9RT, UK. [9,10]. A large part of this increase can be accounted for by lymphocytes (9], although an influx of neutrophils into the lungs has been observed soon after antigen challenge [10,11].…”

“…[9,10]. A large part of this increase can be accounted for by lymphocytes (9], although an influx of neutrophils into the lungs has been observed soon after antigen challenge [10,11]. Using monoclonal antibodies, a number of workers have demonstrated that most of the BAL lymphocytes expressed T-cell markers, while only a small proportion expressed B-cell related markers [9,12,13].…”

“…A large part of this increase can be accounted for by lymphocytes (9], although an influx of neutrophils into the lungs has been observed soon after antigen challenge [10,11]. Using monoclonal antibodies, a number of workers have demonstrated that most of the BAL lymphocytes expressed T-cell markers, while only a small proportion expressed B-cell related markers [9,12,13]. Analyses of T-cell subsets from these patients have shown that CD8+ lymphocytes are the predominant cells with a resulting inversion of the CD4:CD8 ratio [14-17] and similar observations have been made in animal models [18,19).…”

“…These include increased numbers of CD57+ (HNK-1) and CD56+ (NK.H-1) cells and the number of such cells also eo-expressing T-cell markers predominates over the number of cells lacking these determinants. The surface membrane of these BAL cells, however, appear to lack other markers which strictly define NK cells [9]. Further evidence for cytotoxicity has been found by evaluating the relative proportions of BAL T-cells expressing the y/A or a/~ chains of the T-cell receptor.…”

“…With regard to functional activity both cytotoxic and suppressor in vitro function has been demonstrated [9,25,26). A significant increase in spontaneous cytotoxicity has been observed in patients with hypersensitivity pneumonitis [25], whereas BAL lymphocytes from exposed but asymptomatic farmers display in vitro cytotoxicity similar to that of controls [9]. Lung T-cells from patients with hypersensitivity pneumonitis have also been found to display in vitro suppressor activity [9,26].…”