Kaplan G, Weinstein D E, Steinman R M, Levis W R, Elvers U, Patarroyo M E, Cohn Z A
J Exp Med. 1985 Sep 1;162(3):917-29. doi: 10.1084/jem.162.3.917.
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.
在瘤型麻风病中，麻风分枝杆菌在真皮巨噬细胞内大量复制。这种缺乏微生物抗性的情况被归因于对麻风分枝杆菌抗原的细胞介导免疫反应存在缺陷。我们检测了T细胞对麻风分枝杆菌的体外反应，以确定低反应性是否可以逆转。该研究纳入了40名来自纽约和哥伦比亚的未经挑选的患者，大多数患有严重的瘤型麻风病。我们首先注意到瘤型麻风病患者有两种类型：一类患者通过T细胞增殖和免疫（γ）干扰素（IFN-γ）释放评估无反应能力；另一类患者相对于结核样型对照表现出低但可检测到的反应。当比较外源性重组白细胞介素-2（IL-2）对两组患者对麻风分枝杆菌抗原反应的影响时，许多低反应者（而非无反应者）表现出增殖增强和IFN-γ释放增加。为了评估单核细胞可能的抑制作用，用细胞特异性单克隆抗体和补体清除这些细胞。单核细胞的清除常常使已有的微弱反应增强，但并未逆转麻风分枝杆菌无反应者的无反应状态。这种增强并非麻风分枝杆菌特异性的，因为当卡介苗作为增殖和IFN-γ产生的抗原刺激物时也观察到了这种情况。用OKT8抗体和补体清除抑制性T细胞亚群也未能恢复无反应患者的反应。我们得出结论，相当数量的瘤型麻风病患者对麻风分枝杆菌表现出低度反应性，并且这些反应在体外可通过IL-2或单核细胞清除而增强。然而，无反应状态无法逆转。由于目前可用的检测方法测量的是先前致敏T细胞的功能，抑制机制可能仍通过损害对麻风分枝杆菌抗原的初始致敏而导致细胞介导免疫缺陷。
