Immunophenotyping of bronchoalveolar lavage lymphocytes.

Abstract

The lung is continuously exposed to the external environment and its mixtures of complex antigens through the air we breathe. It is estimated that the resting human adult inhales 12,000 liters of air each day, while even mild physical activity can double or triple this amount (85). In addition to anatomical barriers, such as airway angulation, mucociliary clearance, and coughing, both humoral and cellular defense mechanisms play an important role in maintaining the viability of the host. One of the first lines of defense against particulate matter is mucociliary clearance and phagocytic activity of alveolar macrophages. Antigen entering the pulmonary tract encounters antigen-presenting cells comprised of alveolar and interstitial macrophages and effector T lymphocytes (reviewed in reference 1). This encounter leads to a complex sequence of events that results in cell migration and activation at a site of inflammation, with the subsequent development of lymphocyte functional effector activity. After many years of study there is still a paucity of information on the origin, half-life, fate, and specific function of pulmonary lymphocytes in health and disease (80). Protective immunity against inhaled antigens is mediated by the lymphocytes that are localized to the surface of the respiratory tract. The compartments in the lung where lymphocytes are present are (i) the epithelium and lamina propria of the air-conducting regions, (ii) the bronchus-associated lymphoid tissue (BALT), which is found commonly in certain animals, i.e., rabbit and rats, (iii) the pulmonary interstitium and vascular beds, and (iv) the bronchoalveolar space. Lymphocytes present in the mucociliary epithelium of the trachea and bronchi are mainly CD8+ T cells. In the bronchial epithelium Fournier et al. (34) found 18 T cells per 100 epithelial cells but essentially no B cells. About 1% of these T cells express the γδ T-cell receptor (31). In contrast to the epithelium, the bronchial lamina propria contains more CD4+ than CD8+ T cells. The majority of these T cells express the memory marker of CD45RO (25). Also, this area shows more surface immunoglobulin-bearing lymphocytes (54). In the human, in contrast to rabbits and rats, BALT is present at birth but disappears in the adult lung. However, after certain stimuli such as cigarette smoking, BALT can develop in adults (90). In the whole human lung interstitium Holt et al. (51) calculated 10 × 109 lymphocytes, a number equivalent to the number of lymphocytes present in human circulating blood. Lymphocytes in the bronchoalveolar space are the most easily accessible of the lymphocytes in the human lung. It has been estimated that the total number of these lymphocytes on the air side of the epithelium is between 2 × 108 and 4 × 108 (22, 54). This number represents about 5% of the total circulating lymphocyte pool in humans or about 5% of the size of the interstitial lung pool.