Document 1176
 DOCN  M9591176
 TI    Functional 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.
 DT    9509
 AU    Howe RC; Wondimu A; Demissee A; Frommel D; Armauer Hansen Research
       Institute, Addis Ababa, Ethiopia.
 SO    Immunology. 1995 Apr;84(4):585-94. Unique Identifier : AIDSLINE
       MED/95309969
 AB    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.
 DE    Antigens, CD3/IMMUNOLOGY  Cells, Cultured  Clone Cells/IMMUNOLOGY
       Cytokines/*BIOSYNTHESIS  CD4-Positive T-Lymphocytes/*IMMUNOLOGY  Human
       Leprosy/*IMMUNOLOGY  Lymphocyte Transformation/IMMUNOLOGY
       Skin/*IMMUNOLOGY  Support, Non-U.S. Gov't  T-Lymphocyte
       Subsets/*IMMUNOLOGY  Th1 Cells/IMMUNOLOGY  Th2 Cells/IMMUNOLOGY  Time
       Factors  JOURNAL ARTICLE

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