The epidermal changes that occur in human cutaneous immune responses have been investigated in the tuberculin reaction and in the lesions of tuberculoid and lepromatous leprosy and cutaneous leishmaniasis. In each situation, there was a dermal accumulation of monocytes and T cells, and the epidermis exhibited thickening. In the tuberculin response, the thickness of the epidermis sometimes doubled in 48-72 hr, and this was attributed to increases in both size and number of keratinocytes. In addition, the phenotype of the keratinocytes changed from la-to Ia'.Similar changes in keratinocyte Ia-antigen expression occurred in the epidermis overlying untreated tuberculoid leprosy and cutaneous leishmaniasis lesions, but not in lepromatous leprosy. We suggest that one or more epidermal growth factors may be generated in the course of a delayed immune reaction in the dermis.The cutaneous lesions of lepromatous leprosy are characterized by a sparse lymphocytic infiltrate and foamy macrophages laden with Mycobacteria leprae. In contrast, tuberculoid leprosy lesions exhibit large numbers of lymphocytes, granuloma formation, and the absence of appreciable numbers of intracellular bacteria (1, 2). Monoclonal antibodies to human leukocytes and their subsets have been used to determine the phenotype of the cells in dermal infiltrates (3-6). These studies showed that in lepromatous lesions there is not only a marked reduction in the numbers of T cells (compared to tuberculoid lesions) but also a selective absence of T lymphocytes of the OKT4+ subset.We wanted to establish whether this represented a specific unresponsiveness to M. leprae antigens or a more general defect in the emigration and accumulation of OKT4+ T cells. For this purpose we generated tuberculin reactions in the dermis of lepromatous patients by use of the purified protein derivative of tuberculin (PPD). During the course of these studies, we observed striking changes in the thickness and Ia-antigen expression of the epidermis overlying the PPDinduced delayed-type hypersensitivity (DTH) lesions. Similar changes also occur in the epidermis overlying the lesions of patients with tuberculoid leprosy and cutaneous leishmaniasis.
MATERIALS AND METHODSThe Generation of DTH Response to PPD. After informed consent was obtained, we evaluated the DTH response to 5 units of PPD in 90 Indian leprosy patients from New Delhi (a highly endemic area for tuberculosis). The study group included 25 lepromatous (LL) (see diagnosis below), 10 borderline lepromatous (BL), and 55 tuberculoid (BT and TT) patients and 50 non-leprosy control individuals. Sex and age distribution were as follows: BL and LL patients, 3 female and 32 male, ages 16-68 (median 30) years; BT and TT patients, 12 female and 43 male, ages 11-68 (median 30) years; non-leprosy controls, 15 female and 35 male, ages 15-65 (median 28) years. The leprosy patients were examined in collaboration with A. K. Sharma and R. S. Mishra (Department of Dermatology, Safdarjung Hospital, New Delhi). Antigen was injected i...