Background: T cells of intraepithelial phenotype have previously been detected in bronchoalveolar lavage (BAL) fluid in a range of lung diseases; these cells express the adhesion molecule α E β 7 integrin, CD103, the ligand for epithelial cell E-cadherin. In subjects with asthma CD4+ lymphocytes are the predominant T cell subtype found in bronchial biopsy specimens and in BAL fluid, whereas CD8+ lymphocytes have been shown to predominate in subjects with chronic obstructive pulmonary disease (COPD). The aim of this study was to analyse the expression of CD103, activation markers (CD25 and CD69), and chemokine receptors (CXCR3, CCR5 and CCR3) on CD4+ and CD8+ lymphocytes from sputum and peripheral blood of subjects with asthma, COPD, and healthy controls. Methods: T cell surface markers were assessed by immunofluorescence labelling and flow cytometry of gated lymphocytes among CD45+ leucocytes in sputum cell suspensions. Results: Sputum lymphocytes expressed higher levels of CD103 and CD69 than blood lymphocytes in all subject groups, with CD103 expressed at higher levels on CD8+ than on CD4+ cells. There were no detectable differences in numbers of CD4+ and CD8+ T cells between subjects with asthma, COPD and controls. The percentage of sputum lymphocytes expressing CXCR3 was lower in subjects with asthma or COPD than in healthy controls; CCR3 was not detectable on sputum or blood lymphocytes. Conclusions: Sputum T lymphocytes are predominantly of activated intraepithelial phenotype (CD103+ CD69+), and normal numbers of CD4+ and CD8+ T cell populations are found in the sputum of patients with asthma and COPD.

No abstract

Descriptive studies have shown an association between eosinophils, interleukin (IL)-5 and pathophysiological processes in patients with atopic asthma. These observations have led to an interest in the eosinophil as the pathogenic cell responsible for many of the clinical features of asthma including symptoms of wheeze, shortness of breath and cough, along with the physiological events such as airway hyperresponsiveness (AHR) and changes in lung function. IL-5 is one of the key cytokines responsible for eosinopoiesis in the bone marrow, along with recruitment and survival of eosinophils in the tissues. In view of this, IL-5 has been an attractive target for the development of anti-IL-5 monoclonal antibodies, inhibiting its action. The results of preclinical studies are viewed as encouraging. Preclinical development involved studies in mice, guinea-pigs and cynomolgus monkeys, with conflicting results in terms of changes in blood and bronchoalveolar lavage eosinophils, AHR and pulmonary resistance. These may be attributed to interspecies differences and to the different models used. Monoclonal antibodies directed against IL-5 have been used in at least four studies involving patients with asthma. Those preliminary studies have shown clear reductions in both blood and sputum eosinophils but no significant changes in physiological parameters of AHR, the late asthmatic reaction or in lung function or symptoms. As in the animal studies, these results suggest a dissociation between eosinophils, AHR, lung function and symptoms of asthma, which may be explained by the multitude of cells involved in the pathogenesis of asthma.

There have been many recent advances in therapeutic approaches to systemic lupus erythematosus (SLE). The roles of cyclophosphamide, hydroxychloroquine, methotrexate and hormonal treatments in the management of SLE have been investigated in recent randomised controlled trials (1). However, although these pharmacological agents have a role to play in some patients with lupus, broad based effects have led to problems with side effects and adverse reactions. For this reason, more specific therapies are urgently required. Such strategies currently under evaluation include altering the cytokine balance, reducing T cell activation and inducing tolerance, blocking T cell costimulatory molecules, reducing auto-antibody production from B cells, targetting specific genes and stem cell transplantation. These are known as "biological" treatments as their aim is to alter patho-physiological processes occurring in the diseased state. This review will focus on the biological therapies currently under investigation-with particular attention on the cytokine-directed therapies.