Bcl

CD8 nella Patologia Polmonare

Nella sarcoidosi i linfociti T associati al granuloma epitelioide sono prevalentemente CD4+ e sono rari i linfociti CD8+ presenti all'interno delle formazioni granulomatose.

Incremento significativo dei linfociti CD8+ è di frequente riscontro nella Alveolite allergica estrinseca (polmonite da ipersensibilità), nel lavaggio broncoalveolare e su biopsia polmonare.

CD8

J Allergy Clin Immunol 2001 Nov;108(5 Part 1):661-70

Hypersensitivity pneumonitis: Current concepts and future questions.

Patel AM, Ryu JH, Reed CE.

Department of Internal Medicine, Divisions of Pulmonary and Critical Care Medicine and Allergic Diseases, Mayo Clinic.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) caused by inhaled allergens can progress to disabling or even fatal end-stage lung disease. The only truly effective treatment is early recognition and control of exposure. Although patients produce antibody exuberantly, the immunopathogenesis involves cellular immunity-notably, CD8(+) cytotoxic lymphocytes, multinucleate giant cell granulomas, and ultimately interstitial fibrosis. Many causative agents have been recognized in occupational dusts or mists, but most current new cases arise from residential exposure to pet birds (pigeons and parakeets), contaminated humidifiers, and indoor molds. The symptoms and physical findings are nonspecific. Serum IgG containing high titers of specific antibody to the offending antigen is elevated. Pulmonary function tests show restrictive and diffusion defects with hypoxemia, especially after exercise. Occasionally, small airways disease causes obstruction. Radio-graphic changes vary according to the stage of the disease and are best evaluated by means of high-resolution computed tomography. In typical cases, the history of a known exposure and the presence of a characteristic interstitial lung disease with serologic confirmation of IgG antibody to the offending antigen suffice for diagnosis. In more obscure cases, observation of changes after a natural environmental exposure, bronchoalveolar lavage, and lung biopsy might be indicated. Among the many questions that remain are the following: What is the prevalence of hypersensitivity pneumonitis and how often is it the cause of chronic interstitial fibrosis? What is the long-term prognosis? Why do most individuals exposed to these antigens develop a vigorous antibody response whereas only a few develop the disease? How does exposure to endotoxin and cigarette smoking affect the disease? To answer these questions, standardized and validated clinical laboratory immunochemical tests are needed, in addition to a systematic approach to diagnosis, classification of disease severity, risk assessment, and management. This review is limited to the disease caused by airborne allergens and focuses on its immunopathogenesis, eliciting agents, clinical manifestations, diagnosis, management, and prognosis.

Curr Opin Pulm Med 1999 Sep;5(5):299-304

A new look at hypersensitivity pneumonitis.

Ando M, Suga M, Kohrogi H.

First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.

Hypersensitivity pneumonitis is an immunologically induced lung disease. Although both immune complex-mediated immune response and T cell-mediated immune response are involved in the pathogenesis of the disease, recent studies show the latter mechanism to be more important. As for T cell-mediated immune response, Th1/Th2 and Tc1/Tc2 cytokines produced by CD4+ and CD8+ T cells play important roles in the development of granulomatous inflammation in the lung, a pathologically characteristic feature of the disease. The critical distinction between CD4+ and CD8+ T cells pertains to recognition of antigens presented by different major histocompatibility complex molecules. Serum levels of KL-6 and soluble intercellular adhesion molecule-1 in patients with HP are useful markers of the disease activity. The chronic form of HP can be difficult to diagnose, and provocation testing is helpful. Erythromycin might be useful for anti-inflammatory therapy.

: J Allergy Clin Immunol 1988 Oct;82(4):577-85; Longitudinal study of alveolitis in hypersensitivity pneumonitis patients: an immunologic evaluation.

Trentin L, Marcer G, Chilosi M, Zambello R, Agostini C, Masciarelli M, Bizzotto R, Gemignani C, Cipriani A, Di Vittorio G, et al.

Padua University School of Medicine, Department of Clinical Medicine, Italy.

Cells recovered from bronchoalveolar lavage were studied, both from a phenotypic and functional point of view, in 18 patients with hypersensitivity pneumonitis (HP) during a prolonged follow-up. A series of monoclonal antibodies against different lymphocyte subpopulations, including T cells, T cell subsets, and natural killer (NK) cells have been used. In some cases, an immunohistologic analysis of lung tissue sections has also been performed. The NK activity has been evaluated with regard to the in vitro function. At the time of the first evaluation, a high number of CD8+ cells with an imbalance of CD4/CD8 ratio had been demonstrated in patients with HP. Consecutive bronchoalveolar lavage evaluations demonstrated a persistent increase of CD8+ cells and a reversal of CD4/CD8 ratio in patients who continued to be regularly exposed to etiologic antigens at work (W+). In the same cases, a persistent increase of NK cells was demonstrated. Cytotoxic cells demonstrated a persistently enhanced in vitro lytic function during the follow-up, even though there appeared to be a trend toward the normal range. Patients who continued to live in agricultural environments but were not further exposed to specific antigens at work (W-) exhibited a recovery of CD4+ cells, a decrease in CD8+ cells, and an increase of CD4/CD8 ratio to the normal range 6 months after the first observation. Immunohistologic analysis, performed at the time of the first evaluation, demonstrated a diffuse infiltration of lung parenchyma by CD8+ cells, both in W+ and W- patients.

Am Rev Respir Dis 1985 Aug;132(2):400-4

Bronchoalveolar lavage and lung histology. Comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.

Semenzato G, Chilosi M, Ossi E, Trentin L, Pizzolo G, Cipriani A, Agostini C, Zambello R, Marcer G, Gasparotto G.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

J Immunol 1986 Aug 15;137(4):1164-72

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

Semenzato G, Agostini C, Zambello R, Trentin L, Chilosi M, Pizzolo G, Marcer G, Cipriani A.

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.