02943nas a2200325   4500000000100000008004100001260001300042653001600055653003100071653002000102653001600122653001400138653001100152653001200163653002600175653000900201653002500210653001400235653001400249653001700263100001300280700001400293700001500307700001400322245016700336300001100503490000700514520208200521022001402603       1995                            d  c1995 Apr10aCD3 Complex10aCD4-Positive T-Lymphocytes10aCells, Cultured10aClone Cells10aCytokines10aHumans10aleprosy10aLymphocyte Activation10aSkin10aT-Lymphocyte Subsets10aTh1 Cells10aTh2 Cells10aTime Factors1 aHowe R C1 aWondimu A1 aDemissee A1 aFrommel D00aFunctional heterogeneity among CD4+ T-cell clones from blood and skin lesions of leprosy patients. Identification of T-cell clones distinct from Th0, Th1 and Th2.  a585-940 v843 a<p>In the present study we examined the functional properties of T-cell clones reactive with Mycobacterium leprae and other mycobacterial antigens. Clones isolated from the skin lesions and blood of leprosy patients across the spectrum were exclusively CD4+CD8- and expressed the alpha beta T-cell receptor. Substantial heterogeneity in the production of cytokines, in particular interleukin-4 (IL-4), was observed, although no striking correlation with clinical status was apparent. A variety of patterns of cytokine secretion distinct from those of T-helper type-1 (Th1) Th2 or Th0, as defined in murine studies, was evident. Most noteworthy was a large number of clones from skin which secreted neither IL-2 nor IL-4, but large amounts of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). Clones isolated from the blood of leprosy patients had a more restricted cytokine secretion profile, and appeared to resemble more closely previously described patterns, including those of high level production of IL-2 and/or IL-4. Virtually all clones, from either skin or blood, produced high levels of IFN-gamma, and thus many clones were IL-4 and IFN-gamma co-producers. The pattern of cytokine production by skin-derived T-cell clones was significantly affected by the in vitro activation status of the cells. Cells enriched in activated blasts tended to produce more IL-4 than small resting cells. In addition, the production of IFN-gamma by skin T-cell clones after < or = 10 weeks of culture was strikingly distinct from that of these clones after 5 months of culture. IL-4 and IFN-gamma co-producing clones shifted to a Th2-like pattern with much less IFN-gamma secretion, whereas non-IL-4-producing clones secreted much higher levels of IFN-gamma after prolonged culture, and became much more Th1-like. However, there was still no correlation between clinical status and pattern of cytokines produced. These results imply that a high fraction of T cells exists in leprosy lesions that is distinct from or that has not yet fully matured into Th1 or Th2 cells.</p>  a0019-2805