Diversity in migration of CD4 and CD8 lymphocytes in different microanatomical compartments of the skin in the tuberculin reaction in man.

The lymphocytes in the perivascular foci of tuberculin skin tests have a similar CD4:CD8 ratio to those in the peripheral blood, suggesting that these subsets do not show bias in their initial emigration. By contrast, the diffusely infiltrating lymphocytes show a relative preponderance of CD4 cells which is progressively greater in successive 250 micron layers into the dermis. A generally similar pattern is seen in healthy controls and in patients with untreated pulmonary tuberculosis, treated leprosy, haemophilia A and chronic obstructive lung disease (COLD) patients treated with prednisolone, but the gradient of increasing CD4:CD8 ratio with depth into the dermis is significantly less steep in patients with tuberculosis, haemophilia and prednisolone-treated COLD than in the healthy controls. Selective migration results in a relative preponderance of CD4 cells in the diffuse infiltrate and it is suggested that this is a mechanism likely to potentiate defensive reaction to Mycobacterium tuberculosis: any deficiency in selective migration may make immunological defences less effective and so contribute to the chronicity of the lesions of tuberculosis.

The cellular responses of tuberculosis and leprosy patients and of healthy controls in skin tests to 'new tuberculin' and leprosin A.

The density and distribution of T4 and T8 lymphocytes and of monocyte/macrophages at the site of skin tests with mycobacterial antigens was studied in pulmonary tuberculosis and leprosy patients and in healthy controls. Most of the inflammatory cells were located in perivascular and periappendicular foci in the dermis: the percentage of the dermis occupied by focal infiltrate was unrelated to the clinical measurement of the area of induration. There was a less intense diffuse infiltrate in the dermis between the foci, most marked in the papillary dermis and lessening progressively in deeper layers. In patients, diffusely infiltrating lymphocytes were more numerous (mainly due to an excess of T8 cells) in relation to extracts of the pathogen causing their disease than to extracts of the other organism: T8 cells were particularly numerous in reactions to Leprosin A in three of four partly treated leprosy patients who had been classified as tuberculoid at the time of diagnosis. The density of diffusely infiltrating macrophages showed a similar density gradient and selective concentration in response to active disease pathogens. However these cells were less numerous in partly treated leprosy patients than in controls and most frequent in untreated pulmonary tuberculosis patients. Selective migration of monocyte/macrophages and, to a lesser extent T8 cells, appears to be a prominent feature in the reaction of patient with active mycobacterial disease to antigens derived from the causative organisms: this suggests that it might become possible to distinguish direct reactions from cross-reactions in human delayed hypersensitivity reactions by identification of these histological features.