The interaction of LCK and the CD4 co-receptor alters the dose response of T-cells to interleukin-7.
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.
Kittipatarin
Christina
C
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, United States.
Tschammer
Nuska
N
Khaled
Annette R
AR
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D003001:Cloning, Molecular; D004306:Dose-Response Relationship, Immunologic; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D011485:Protein Binding; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes / Q000235:genetics
D015704:CD4 Antigens; D015851:Interleukin-7; D050799:STAT5 Transcription Factor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)