FUNCTIONAL-HETEROGENEITY AMONG CD4(-CELL CLONES FROM BLOOD AND SKIN-LESIONS OF LEPROSY PATIENTS, IDENTIFICATION OF T-CELL CLONES DISTINCT FROM TH0, TH1 AND TH2() T)

In the present study we examined the functional properties of T-cell c lones reactive with Mycobacterium leprae and other mycobacterial antig ens. Clones isolated from the skin lesions and blood of leprosy patien ts across the spectrum were exclusively CD4(+)CD8(-) and expressed the alpha beta T-cell receptor. Substantial heterogeneity in the producti on of cytokines, in particular interleukin-4 (IL-4), was observed, alt hough no striking correlation with clinical status was apparent. A var iety of patterns of cytokine secretion distinct from those of T-helper type-1 (Th1) Th2 or Th0, as defined in murine studies, was evident. M ost noteworthy was a large number of clones from skin which secreted n either 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, incl uding those of high level production of IL-2 and/or IL-4. Virtually al l 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 patte rn of cytokine production by skin-derived T-cell clones was significan tly affected by the in vitro activation status of the cells. Cells enr iched in activated blasts tended to produce more IL-4 than small resti ng cells. In addition, the production of IFN-gamma by skin T-cell clon es after less than or equal to 10 weeks of culture was strikingly dist inct 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 les s IFN-gamma secretion, whereas non-IL-4-producing clones secreted much higher levels of IFN-gamma after prolonged culture, and became much m ore 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 fr om or that has not yet fully matured into Th1 or Th2 cells.