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 and maintenance of a T(h)2 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.
National Heart and Lung Institute, Imperial College School of Medicine, Norfolk Place, London W2 1PG, UK.
L A
LA
Stanciu
K
K
Roberts
L C
LC
Lau
A J
AJ
Coyle
S L
SL
Johnston
D000328:Adult; D001249:Asthma / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000378:metabolism; D017730:Ki-1 Antigen / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D018106:CD28 Antigens; D019013:CD40 Antigens; D015848:Interleukin-5; D017730:Ki-1 Antigen; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E