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

Repeated administration or chronic presence of antigen during CD4(+) T cell activation and a cytokine milieu enriched in IL-4 favour the generation an d maintenance of a T(h)2 population. However, there is little data on how t hese 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. Rep eated 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 a ctivity and provided help to resting a cells for IgE synthesis, The presenc e of exogenous IL-4 during repeated stimulation further increased the numbe r 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 t he growth of cells with a type 2 phenotype and that this was further amplif ied by the presence of IL-4, These mechanisms may be important in virus-ind uced lung eosinophilic inflammation in healthy subjects and virus-induced e xacerbations of asthma.