02970nas a2200409   4500000000100000008004100001260001600042653002400058653001200082653002900094653002400123653002000147653002400167653002100191653001800212653002500230653002600255653001600281653000900297653002800306653002500334653002500359653003400384100001500418700002000433700001200453700001700465700001800482700001400500700001200514245007700526300001100603490000800614050001500622520190900637022001402546       1991                            d  c1991 Sep 0110aAmino Acid Sequence10aAnimals10aAntigen-Presenting Cells10aAntigens, Bacterial10aHLA-DR Antigens10aHeat-Shock Proteins10aInterferon-gamma10aInterleukin-410aLeprosy, Tuberculoid10aLymphocyte Activation10aLymphokines10aMice10aMolecular Sequence Data10aMycobacterium leprae10aT-Lymphocyte Subsets10aT-Lymphocytes, Helper-Inducer1 aHaanen J B1 aWaal Malefijt R1 aRes P C1 aKraakman E M1 aOttenhoff T H1 aVries R R1 aSpits H00aSelection of a human T helper type 1-like T cell subset by mycobacteria.  a583-920 v174  aHAANEN19913 a<p>Mycobacteria elicit a cellular immune response in their hosts. This response usually leads to protective immunity, but may sometimes be accompanied by immunopathology due to delayed type hypersensitivity (DTH). A striking example in man is tuberculoid leprosy, which is characterized by high cellular immunity to Mycobacterium leprae and immunopathology due to DTH. Skin lesions of patients suffering from this disease have the characteristics of DTH reactions in which macrophages and CD4+ T lymphocytes predominate. In animal models, it has been shown that DTH responses are associated with the presence of a particular subset of CD4+ T cells (T helper type 1 [Th1]) that secrete only certain cytokines, such as interleukin 2 (IL-2), interferon gamma (IFN-gamma), and lymphotoxin, but no IL-4 or IL-5. We studied the cytokine release of activated M. leprae-reactive CD4+ T cell clones derived from tuberculoid leprosy patients. These T cell clones, which were reactive with mycobacterial heat shock proteins, exhibited a Th1-like cytokine secretion pattern with very high levels of IFN-gamma. Half of these clones secreted low levels of IL-4 and IL-5, but the ratio of IFN-gamma to IL-4 and IL-5 was much higher than that of T cell clones reactive with nonmycobacterial antigens. A Th1-like cytokine secretion pattern was also observed for T cell clones and polyclonal T cell lines from control individuals that recognized both heat shock and other mycobacterial antigens. The levels of IFN-gamma secreted by these clones were, however, significantly less than those of patient-derived T cell clones. This Th1-like pattern was not found with T cell clones from the same patients and healthy individuals generated in the same manner, but reactive with nonmycobacterial antigens. Our data thus indicate that mycobacteria selectively induce human T cells with a Th1-like cytokine secretion profile.</p>  a0022-1007