Attenuation of cytokine responsiveness during T cell development and differentiation.
Cytokines play critical roles during T cell development; however, it is unclear to what extent development is altered by the high levels of cytokines produced during immune responses. A potential mechanism to shield developing cells from cytokine influence is attenuation of cytokine signaling. Using intracellular staining and flow cytometry to detect cytokine-induced Stat phosphorylation, we analyzed the cytokine responsiveness of developmentally defined mouse T cells. We assessed CD4(-)CD8(-) (DN), CD4(+)CD8(+) (DP), CD4(+)CD8(-) (SP4), and CD4(-)CD8(+) (SP8) in the thymus, and CD4(+)CD44(lo) (naive), CD4(+)CD44(hi) (memory), CD8(+)CD44(lo) (naive), and CD8(+)CD44(hi) (memory) in the periphery for responsiveness to interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL- 10, IL-15, interferon-alpha (IFN-alpha), and IFN-gamma. SP thymocytes responded to a wider range of cytokines than did the less mature DN and DP subpopulations. DP thymocytes were nonresponsive to all cytokines tested except for modest responses to IL-4 and IFN-alpha. Peripheral naive and memory T cells also displayed differential cytokine sensitivity. Memory T cells were less responsive to the proinflammatory cytokines IL-6 and IFN-gamma when compared with naive T cells, and the memory CD4(+) subset was less responsive to IL-4. In summary, developing thymocytes and memory T cells appear to be resistant to the influences of numerous cytokines produced during immune responses.
Marino
Julie H
JH
University of Oklahoma College of Medicine, Department of Surgery, Tulsa, OK 74135, USA.
Van De Wiele
C Justin
CJ
Everhart
Joshua M
JM
Masengale
Rhonda
R
Naukam
Rebecca J
RJ
Schniederjan
Matthew J
MJ
Vo
Stephen
S
Teague
T Kent
TK
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018121:Receptors, Cytokine / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines; D018121:Receptors, Cytokine; D050791:STAT Transcription Factors