03010nas a2200397   4500000000100000008004100001260001600042653001000058653002400068653001000092653001900102653001100121653001100132653002300143653002100166653001800187653001200205653002600217653000900243653001600252653002400268653002500292653001800317100001300335700001800348700001700366700001400383700001300397700001800410700001300428245007400441300001100515490000800526520206400534022001402598       1985                            d  c1985 Sep 0110aAdult10aAntigens, Bacterial10aChild10aConcanavalin A10aFemale10aHumans10aImmunity, Cellular10aInterferon-gamma10aInterleukin-210aleprosy10aLymphocyte Activation10aMale10aMiddle Aged10aMycobacterium bovis10aMycobacterium leprae10aT-Lymphocytes1 aKaplan G1 aWeinstein D E1 aSteinman R M1 aLevis W R1 aElvers U1 aPatarroyo M E1 aCohn Z A00aAn analysis of in vitro T cell responsiveness in lepromatous leprosy.  a917-290 v1623 a<p>In lepromatous leprosy, there is extensive replication of Mycobacterium leprae (M. leprae) within dermal macrophages. This lack of microbial resistance has been attributed to a defective cell-mediated immune response to M. leprae antigens. We have examined the in vitro response of T cells to M. leprae to determine if hyporesponsiveness could be reversed. The study included 40 unselected patients from New York and from Colombia, most with the severe lepromatous form of the disease. We first noted that lepromatous leprosy patients were of two types: those unable to respond, as assessed by T cell proliferation and immune (gamma) interferon (IFN-gamma) release, and a second group, exhibiting low but detectable responses relative to tuberculoid controls. When the effect of exogenous recombinant interleukin-2 (IL-2) on the response to M. leprae antigens was compared in the two groups, many of the low responders, but not the nonresponders, showed enhanced proliferation and IFN-gamma release. To evaluate a possible suppressive effect of monocytes, these cells were eliminated with a cell-specific monoclonal antibody and complement. Depletion of monocytes often expanded preexisting weak responses but did not reverse the anergy of the M. leprae nonresponders. The enhancement was not M. leprae-specific, since it was also observed when bacillus Calmette-Guerin was the antigenic stimulus for proliferation and IFN-gamma production. Removal of the suppressor T cell subset, with OKT8 antibody and complement, also did not restore responses in nonresponder patients. We conclude that a sizable number of lepromatous leprosy patients exhibit a low degree of responsiveness to M. leprae and that the responses can be enhanced in vitro with IL-2 or with monocyte depletion. Nonresponsiveness, however, cannot be reversed. Since currently available assays measure the function of previously sensitized T cells, suppressor mechanisms may yet contribute to defective cell-mediated immunity by impairing the initial sensitization to M. leprae antigens.</p>  a0022-1007