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International Immunology, Vol. 13, No. 3, 341-348, March 2001
© 2001 Japanese Society for Immunology

Induction of type 2 activity in adult human CD8+ T cells by repeated stimulation and IL-4

Luminita A. Stanciu, Kevan Roberts1,, Laurie C. K. Lau1,, Anthony J. Coyle2, and Sebastian L. Johnston

National Heart and Lung Institute, Imperial College School of Medicine, Norfolk Place, London W2 1PG, UK
1 University Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
2 Millennium Pharmaceuticals, Boston, MA 02139, USA

Correspondence to: S. L. Johnston

Repeated administration or chronic presence of antigen during CD4+ T cell activation and a cytokine milieu enriched in IL-4 favour the generation and maintenance of a Th2 population. However, there is little data on how these factors affect adult human CD8+ T cell functions. We established in vitro conditions to culture purified human CD8+ T cells, and investigated how repeated stimulation and exogenous IL-4 modulated their functions. Repeated TCR–CD3 stimulation of CD8+ T cells increased the number of CD25-, CD30- and CD40 ligand-expressing cells, and their capacity to secrete IL-4 and IL-5. In addition, repeatedly stimulated CD8+ T cells had cytotoxic activity and provided help to resting B cells for IgE synthesis. The presence of exogenous IL-4 during repeated stimulation further increased the number of CD25+ and CD30+ CD8+ T cells, up-regulated the number of IL-5+ cells, and increased IL-5 levels released. These observations demonstrate that repeated TCR–CD3 stimulation of normal human CD8+ T cells favoured the growth of cells with a type 2 phenotype and that this was further amplified by the presence of IL-4. These mechanisms may be important in virus-induced lung eosinophilic inflammation in healthy subjects and virus-induced exacerbations of asthma.

Keywords: cellular differentiation, cytokines, cytotoxic T lymphocyte

Transmitting editor: R. L. Coffman


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