ABSTRACT
There are strong evidences suggesting that Thl and Th2 lymphocytes develop from the same Thlymphocyte precursor under the influence of environmental or genetic factors acting at the level of antigen presentation, but it remains to be answered whether it is possible to change the cytokine profile of established or ongoing Th1 and Th2 response. The purpose of this study is to reveal whether it is possible to reverse the cytokine profile of human Th lymphocytes by the modulation of antigen presentation. Using a multiparameter flow cytometric assay that allows simultaneous determination of surface CD4 and intracellular IFN-r or IL-4, we have studied the emergence of Th1 or Th2 lymphocytes in response to tetanus toxoid exposure and the patterns of cytokine synthesis in established T lymphocyte clones. Th2 populations arising after 4 wk of stimulation in IL-2, PHA, tetanus toxoid and irradiated autogeneic peripheral blood mononuclear cells as antigen presenting cells (APC) could give rise to IFN-r-producing Th1 lymphocytes when stimulated in IL-2 plus PHA in the absence of antigen and APC. These IFN-r-producing Th1 lymphocytes nearly disappeared and IL-4-producing Th2 lymphocytes predominated again when cultured again in the presence of antigen and APC. In contrast, prolonged culture in the absence of antigen and APC induced relative predominance of IFN-r-producing The lymphocytes. The cytokine profile of long-term Th2 population arising originally from the repeated stimulation in the presence of antigen and APC appeared more homogeneous and less reversible, although they could convert to Th1 lymphocytes when cultured without antigen and APC. These findings may explain that the polarized Th response is reversible depending on the presence of antigen presentation.
