Title

The Interaction Of Lck And The Cd4 Co-Receptor Alters The Dose Response Of T-Cells To Interleukin-7

Keywords

Cytokine; Lymphocytes; Signal transduction

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. © 2010 Elsevier B.V.

Publication Date

7-1-2010

Publication Title

Immunology Letters

Volume

131

Issue

2

Number of Pages

170-181

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.imlet.2010.04.007

Socpus ID

77953711887 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/77953711887

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