Regulatory T cell ablation causes acute T cell lymphopenia.
Regulatory T (Treg) cells enforce T cell homeostasis and maintain peripheral T cell tolerance. Here we report a previously unappreciated phenomenon of acute T cell lymphopenia in secondary lymphoid organs and non-lymphoid tissues triggered by Treg cell depletion that precedes the expansion of self-reactive T cells. Lymphopenia affects both neonates and adults indicating a dominant role of Treg cells in maintaining peripheral T cell numbers regardless of the developmental stage. The lymphopenia was neither triggered by caspase-dependent apoptosis nor macrophage-mediated clearance of T cells, nor diminished survival of naïve or recently activated T cells due to paucity of IL-7. It is possible that transient lymphopenia associated with congenital or acute Treg cell deficiency may contribute to the development of T cell mediated autoimmune disorders.
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America ; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Bruno
B
Moltedo
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America ; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Saskia
S
Hemmers
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America ; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Alexander Y
AY
Rudensky
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000502:physiology*; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D008231:Lymphopenia / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015851:Interleukin-7; D012333:RNA, Messenger; D020169:Caspases