Title

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

Authors

Authors

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

Comments

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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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