Canaday D H, Ziebold C, Noss E H, Chervenak K A, Harding C V, Boom W H
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, OH 44106, USA.
J Immunol. 1999 Jan 1;162(1):372-9.
Human immune responses to M. tuberculosis are characterized by activation of multiple T cell subsets including CD4+, CD8+, and gammadelta T cells, and the role of CD8+ alphabeta TCR+ T cells in this response is poorly understood. Stimulation of T cells from healthy tuberculin skin test-positive persons with live M. tuberculosis-H37Ra or soluble M. tuberculosis Ags readily up-regulated IL-2Ralpha (CD25) expression on CD8+ T cells. Purified resting and activated CD8+ T cells produced IFN-gamma and proliferated to both M. tuberculosis bacilli and soluble mycobacterial Ags with monocytes as APC. Precursor frequency of mycobacterial Ag-specific CD8+ T cells by IFN-gamma enzyme-linked immunospot was 5-10-fold lower than the precursor frequency of CD4+ T cells, and IFN-gamma secretion by CD8+ T cells was 50-100-fold lower. CD8+ T cells secreted approximately 10-fold less IFN-gamma per cell than CD4+ T cells in response to mycobacterial Ags. CD8+ T cell responses to M. tuberculosis bacilli were blocked by anti-MHC class I antibody and required Ag processing. Processing of M. tuberculosis bacilli by monocytes for presentation to MHC class I-restricted CD8+ T cells was insensitive to brefeldin A treatment, which blocks the conventional MHC class I Ag-processing pathway. These results represent the first demonstration that human cells can process pathogen Ags via an alternate Ag-processing pathway for MHC class I and suggest a mechanism for participation of IFN-gamma-secreting CD8+ T cells in the human immune responses to M. tuberculosis.
人类对结核分枝杆菌的免疫反应特征为多种T细胞亚群的激活，包括CD4 +、CD8 +和γδ T细胞，而CD8 + αβ TCR + T细胞在这种反应中的作用却知之甚少。用活的结核分枝杆菌-H37Ra或可溶性结核分枝杆菌抗原刺激来自健康结核菌素皮肤试验阳性者的T细胞，可轻易上调CD8 + T细胞上IL-2Rα（CD25）的表达。纯化的静息和活化CD8 + T细胞产生IFN-γ，并以单核细胞作为抗原呈递细胞，对结核分枝杆菌和可溶性分枝杆菌抗原均发生增殖反应。通过IFN-γ酶联免疫斑点法检测，分枝杆菌抗原特异性CD8 + T细胞的前体频率比CD4 + T细胞的前体频率低5至10倍，且CD8 + T细胞的IFN-γ分泌量低50至100倍。在对分枝杆菌抗原的反应中，每个CD8 + T细胞分泌的IFN-γ比CD4 + T细胞少约10倍。CD8 + T细胞对结核分枝杆菌的反应被抗MHC I类抗体阻断，且需要抗原加工。单核细胞对结核分枝杆菌进行加工以呈递给MHC I类限制性CD8 + T细胞，这一过程对布雷菲德菌素A处理不敏感，布雷菲德菌素A可阻断传统的MHC I类抗原加工途径。这些结果首次证明人类细胞可通过MHC I类的替代抗原加工途径处理病原体抗原，并提示了分泌IFN-γ的CD8 + T细胞参与人类对结核分枝杆菌免疫反应的一种机制。
