03223nas a2200481   4500000000100000008004100001260001600042653001000058653004400068653001700112653002500129653001400154653001100168653002300179653001800202653002100220653002500241653002800266653001600294653002500310653001600335653002500351653001500376653002500391653000900416653001800425100001300443700001600456700001800472700001400490700001400504700001200518700001500530700001800545700002000563700001200583245012700595300001200722490000800734050001500742520197000757022001402727       1989                            d  c1989 Mar 0110aAdult10aAntigens, Differentiation, T-Lymphocyte10aCD8 Antigens10aCell Differentiation10aEpidermis10aHumans10aImmunity, Cellular10aInterleukin-210aLangerhans Cells10aLeprosy, lepromatous10aLeukocytes, Mononuclear10aMacrophages10aMicroscopy, Electron10aMiddle Aged10aMycobacterium leprae10aPhagocytes10aRecombinant Proteins10aSkin10aT-Lymphocytes1 aKaplan G1 aKiessling R1 aTeklemariam S1 aHancock G1 aSheftel G1 aJob C K1 aConverse P1 aOttenhoff T H1 aBecx-Bleumink M1 aDietz M00aThe reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2.  a893-9070 v169  aKAPLAN19893 a<p>Human rIL-2 (10-30 micrograms) was injected intradermally into the skin of patients with lepromatous leprosy with high bacillary loads. All patients responded to the lymphokine with local areas of induration that peaked at 24 h and persisted for 4-7 d irrespective of whether the site was "normal skin" or a nodular lesion. Within 24 h there was an extensive emigration of T cells and monocytes into the site. The percentage of the dermis infiltrated by mononuclear cells increased by more than sevenfold, peaking at 4 d and persisting for greater than 15 d. Both CD4+ and CD8+ T cells entered the site. T cells of CD4+ phenotype predominated at 2-7 d but by 11 d, CD8+ cells were predominant. Considerable numbers of T6+ Langerhans' cells appeared in the dermis by 72 h and persisted for 3 wk. By 4 d the thickness of the overlying epidermis had increased twofold, and keratinocytes were expressing MHC class II antigen and the IFN-gamma-induced peptide IP-10. Starting at 48 h, there was an extensive destruction of mononuclear phagocytes that contained structurally intact or fragmented M. leprae observed at the electron microscope level. The organisms, either free or contained within endocytic vacuoles, were discharged into the extracellular space and then reingested by blood-borne monocytes. This was followed by marked reductions in the number of acid-fast organisms in the injected site, evident as early as 4-7 d and more marked at 2-3 wk after injection. 13 of 15 patients exhibited a disposal of acid-fast bacilli ranging from 5- to 1,000-fold with a mean value of approximately 100-fold. The administration of IL-2 leads to the generation of an effective cell-mediated immune response, recapitulating an antigen-driven event and leading to striking local reductions in M. leprae. In comparison with the purified protein derivative of tuberculin reaction, bacilli are cleared more promptly, although emigratory cells persist for a shorter time.</p>  a0022-1007