The interaction of LCK and the CD4 co-receptor alters the dose response of T-cells to interleukin-7

    Authors

    C. Kittipatarin; N. Tschammer;A. R. Khaled

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    Abbreviated Journal Title

    Immunol. Lett.

    Keywords

    CYTOKINE; Lymphocytes; Signal transduction; PROTEIN KINASE P56LCK; SRC FAMILY KINASES; TYROSINE KINASES; HOMEOSTATIC; PROLIFERATION; LYMPHOID DEVELOPMENT; ACTIVATION; IL-7; RECEPTOR; CYTOKINE; MICE; Immunology

    Abstract

    CD8 and CD4 T-cells grow optimally under different concentrations of the cytokine, interleukin-7 (IL-7). While CD8 T-cells expand at high doses of IL-7, CD4 T-cells favor low doses. To examine the reason for the preference of CD4 T-cells for lower doses of the cytokine, we used IL-7 dependent T-cells to study signal transduction upon a range of IL-7 concentrations. We found that the high dose responsiveness of CD8 T-cells to IL-7 could be altered if these cells also expressed CD4. Using the phosphorylation of STAT5 as an indicator of growth, we found that the co-receptor associated kinase, LCK, contributed to phospho-STAT5 levels. Phospho-STAT5 was elevated at high dose IL-7 for CD8 T-cells and at low dose IL-7 for CD4 T-cells, which was reversed upon LCK inhibition. Examining the direct association of LCK with CD4 using a T-cell line that over-expresses CD4, we determined that CD4 could directly sequester LCK. Non-CD4 T-cells were not restricted in this manner and levels of phospho-STAT5 increased proportionally to the IL-7 dose. Our studies, therefore, show that the response of a T-cell to IL-7 can be modulated by the availability of LCK. (C) 2010 Elsevier B.V. All rights reserved.

    Journal Title

    Immunology Letters

    Volume

    131

    Issue/Number

    2

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    170

    Last Page

    181

    WOS Identifier

    WOS:000279703800010

    ISSN

    0165-2478

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