Interleukin-4 downregulates CD127 expression and activity on human thymocytes and mature CD8 super(+) T cells

• Published in: European journal of immunology 2010-05, Vol.40 (5), p.1396-1407
• Main Authors: Crawley, Angela M, Vranjkovic, Agatha, Young, Charlene, Angel, Jonathan B
• Format: Article
• Language: English
• Subjects: Hepatitis C virus; Human immunodeficiency virus
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200940093

Signaling via the IL-7 receptor complex (IL-7R alpha /CD127 and IL-2R gamma /CD132) is required for T-cell development and survival. Decreased CD127 expression has been associated with persistent viral infections (e.g. HIV, HCV) and cancer. Many IL-2R gamma -sharing ( gamma sub(C)) cytokines decrease CD127 expression on CD4 super(+) and CD8 super(+) T cells in mice (IL-2, IL-4, IL-7, IL-15) and in humans (IL-2, IL-7), suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8 super(+) T cells is unknown and was therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested and only on naive (CD45RA super(+)) CD8 super(+) T cells, without altering membrane-bound CD127 mRNA expression. Pre-treatment of thymocytes or CD8 super(+) T cells with IL-4 inhibited IL-7-mediated phosphorylation of STAT5 and decreased proliferation of CD8 super(+) T cells. By downregulating CD127 expression and signaling on developing thymocytes and CD8 super(+) T cells, IL-4 is a potential contributor to impaired CD8 super(+) T-cell function in some anti-viral and anti-tumor responses. These findings are of particular consequence to diseases such as HIV, HCV, RSV, measles and cancer, in which CD127 expression is decreased, IL-7 activity is impaired and IL-4 concentrations are elevated.