Injury induces early activation of T-cell receptor signaling pathways in CD4+ regulatory T cells.
Although it is known that injury enhances the regulatory activity of CD4 regulatory T cells (Tregs), the cellular and molecular mechanisms responsible for injury-induced Treg activation remain unclear. This study was designed to investigate and compare injury-induced T-cell receptor (TCR) signaling in Tregs, non-Tregs, and CD8 T cells. Specifically, we used phospho-flow cytometry to measure the expression and phosphorylation of ZAP-70, protein kinase C θ, nuclear factor of activated T cells, and glycogen synthase kinase 3β in FoxP3 Tregs versus FoxP3 non-Tregs versus CD8 T cells. Groups of male C57BL/6J mice underwent burn or sham injury, and lymph nodes and spleens were harvested at early time points-15, 30, 60, 120, and 240 min-to measure TCR signaling. As early as 15 min after burn injury, we observed a significant upregulation and phosphorylation of ZAP-70, protein kinase C θ, nuclear factor of activated T cells, and glycogen synthase kinase 3β in Tregs prepared from injury-site-draining lymph nodes. Burn injury did not activate TCR signaling in Tregs from the spleen or in CD4 non-Tregs and CD8 T cells. In conclusion, the results of this study demonstrate that burn injury activates TCR signaling in Tregs, but not non-Tregs or CD8 T cells. These findings suggest that injury provides an early TCR-activating signal to Tregs and supply new insights into how injury influences the adaptive immune system.
Hanschen
Marc
M
Department of Surgery (Immunology), Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
Tajima
Goro
G
O'Leary
Fionnuala
F
Ikeda
Kimiko
K
Lederer
James A
JA
D000818:Animals; D002056:Burns / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D051858:Forkhead Transcription Factors; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D050778:NFATC Transcription Factors; D011493:Protein Kinase C; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099221:Protein Kinase C zeta; C498833:Foxp3 protein, mouse; C497262:Zap70 protein, mouse; C000605507:Gsk3b protein, mouse