International Immunology, Vol. 11, No. 4, 593-603,
April 1999
© 1999 Japanese Society for Immunology
Differentiation of human single-positive fetal thymocytes in vitro into IL-4- and/or IFN-
-producing CD4+ and CD8+ T cells
1 Department of Human Immunology, DNAX Research Institute, CA 94304, USA
2 Present address: First Department of Medicine, Hokkaido University, Sapporo 060, Japan
3 Present address: Novartis Research Institute, Vienna 1235, Austria
4 Present address: INSERM U454, 34259 Montpellier, France
Correspondence to: H. Yssel, INSERM U454, CHU Arnaud de Villeneuve, 371, Avenue Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France
In this study we have investigated the capacity of human fetal thymocytes to differentiate in vitro into subsets of T cells with polarized Th1 or Th2 cytokine profiles. Stimulation of freshly isolated human fetal thymocytes with anti-CD3 mAb, cross-linked onto CD32,CD58,CD80-expressing mouse fibroblasts and subsequent culture in the presence of exogenous rIL-2 for 6 days, induced the production of both IL-4 and IFN-
, which was mainly produced by CD4+ single-positive (SP) and CD8+ SP cells respectively. Addition of rIL-4 during priming augmented IL-4 production in cultures of human fetal thymocytes, which was mainly due to an increased production of IL-4 by CD8SP cells. In contrast, addition of IL-4 to the cultures only slightly enhanced IL-4 production and had little effect on frequencies of IL-4-producing CD4SP cells. Both CD4SP and CD8SP cells produced IL-5, IL-10 and IL-13 at comparable levels, following priming in the presence of rIL-4. Priming in the presence of rIL-12 strongly enhanced the production of IFN- in both CD4SP and CD8SP cells. No correlation between expression of CD27, CD30 and CD60, and a particular cytokine profile of differentiated thymocytes could be demonstrated. Together, these results demonstrate the full capacity of fetal human thymocytes to differentiate into cytokine-producing T cells in a priming milieu with appropriate stimulatory molecules and exogenous cytokines. In addition, CD4SP thymocytes rapidly differentiate into polarized Th2 cells following stimulation in vitro in the absence of exogenous rIL-4.
Keywords: cellular differentiation, cytokines, FACS, human, Th1, Th2, thymocytes
Transmitting editor: K.-i. Arai
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