Mshana R N, Hastings R C, Krahenbuhl J L
Laboratory Research Branch, Gillis W. Long Hansen's Disease Center, Carville, Louisiana.
Immunobiology. 1988 Apr;177(1):40-54. doi: 10.1016/S0171-2985(88)80090-1.
Both antigen-specific and non-specific anergy are common features of disseminated mycobacterial infections, and the pathogenesis of such anergy is as yet not fully understood. To date, most studies have focused on the efferent limb of the immune response, and no detailed information is available on the early macrophage-T cell interaction and its consequence on T cell clonal proliferation. To gain information on this crucial phase of mycobacteriosis, we have conducted studies to evaluate the effect of M. kansasii infection on Ia expression induced by T cell-derived lymphokine and have assessed whether such cells can adequately present either mycobacterial or allogeneic antigens to T cells. In vitro infection of mouse resident peritoneal macrophages with live but not heat-killed M. kansasii resulted in a significantly reduced percentage of cells expressing monoclonal antibody detectable Ia antigen following optimal stimulation with crude lymphokine preparations or recombinant mouse gamma interferon. In parallel experiments, macrophages infected with the mycobacteria were co-cultured with syngeneic in vivo M. kansasii sensitized non-adherent, nylon-wool purified lymph node cells, and lymphoproliferation was measured by [3H]thymidine incorporation. It was shown that in co-cultures with macrophages infected with live M. kansasii, the lymphocyte proliferation was marked even in very low infection ratios. In contrast, the response to heat-killed bacilli was dose dependent, reaching peak levels only in high infection ratios. The ability of infected macrophages to present allogeneic antigens was assessed using the mixed leukocyte reaction. Macrophages infected with heat-killed M. kansasii were able to induce a mixed leukocyte reaction similar to uninfected macrophages whereas macrophages infected with live M. kansasii were unable to stimulate allogeneic T cells. These findings may have implications on immunological disturbances often seen in mycobacterial infections, such as leprosy, in which there can be large numbers of non-toxic viable intracellular bacilli.
抗原特异性无反应性和非特异性无反应性都是播散性分枝杆菌感染的常见特征，而这种无反应性的发病机制尚未完全明了。迄今为止，大多数研究都集中在免疫反应的传出支，尚无关于早期巨噬细胞 - T细胞相互作用及其对T细胞克隆增殖影响的详细信息。为了获取有关分枝杆菌病这一关键阶段的信息，我们开展了研究，以评估堪萨斯分枝杆菌感染对T细胞衍生淋巴因子诱导的Ia表达的影响，并评估此类细胞是否能够将分枝杆菌或同种异体抗原充分呈递给T细胞。用活的而非热灭活的堪萨斯分枝杆菌对小鼠驻留腹膜巨噬细胞进行体外感染，在用粗制淋巴因子制剂或重组小鼠γ干扰素进行最佳刺激后，表达单克隆抗体可检测的Ia抗原的细胞百分比显著降低。在平行实验中，将感染分枝杆菌的巨噬细胞与体内对堪萨斯分枝杆菌致敏的同基因非贴壁、尼龙毛纯化的淋巴结细胞共培养，通过[3H]胸腺嘧啶核苷掺入法测定淋巴细胞增殖。结果显示，在与感染活堪萨斯分枝杆菌的巨噬细胞共培养时，即使感染比例非常低，淋巴细胞增殖也很明显。相比之下，对热灭活杆菌的反应呈剂量依赖性，仅在高感染比例时达到峰值水平。使用混合淋巴细胞反应评估感染巨噬细胞呈递同种异体抗原的能力。感染热灭活堪萨斯分枝杆菌的巨噬细胞能够诱导与未感染巨噬细胞相似的混合淋巴细胞反应，而感染活堪萨斯分枝杆菌的巨噬细胞则无法刺激同种异体T细胞。这些发现可能对分枝杆菌感染（如麻风病）中常见的免疫紊乱具有启示意义，在麻风病中可能存在大量无毒的活细胞内杆菌。
