03073nas a2200385   4500000000100000008004100001260001300042653001200055653001400067653004100081653001100122653002100133653001300154653002100167653001200188653001600200653001600216653000900232653001400241653002500255653000900280100001300289700001300302700001400315700001200329700001500341700001400356700001500370700001300385245012300398300001100521490000800532520213300540022001402673       1987                            d  c1987 Aug10aAnimals10aEpidermis10aHistocompatibility Antigens Class II10aHumans10aInterferon-gamma10aKinetics10aLangerhans Cells10aleprosy10aLymphocytes10aMacrophages10aMice10aMonocytes10aRecombinant Proteins10aSkin1 aKaplan G1 aNusrat A1 aSarno E N1 aJob C K1 aMcElrath J1 aPorto J A1 aNathan C F1 aCohn Z A00aCellular responses to the intradermal injection of recombinant human gamma-interferon in lepromatous leprosy patients.  a345-530 v1283 a<p>The local response to a single intradermal injection of 10 micrograms recombinant gamma-interferon (rIFN gamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 micrograms rIFN gamma at another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm punch biopsies were obtained and examined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation, and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell accumulation peaked at 72 hours but then persisted for 5-7 days. Only small numbers (one-third or less of total T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFN gamma led to a more intense accumulation of cells. Ten micrograms of rIFN gamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24-48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidermis exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFN gamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably sloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells.</p>  a0002-9440