Regulation of CD8+ cytolytic T lymphocyte differentiation by a cholinergic pathway.
In this report, we provide evidence that muscarinic receptors play a role in the generation of CD8+ cytolytic T lymphocytes. Analysis of mice with targeted deletions of each of the known muscarinic receptors (M1-M5) showed that CD8+ T cells from M1 receptor-deficient mice had a defect in the ability to differentiate into cytolytic T lymphocytes. Additional pharmacological experiments support the role of muscarinic receptors in wild type mice and suggest that acetylcholine may be involved. Together, these findings suggest that the M1 muscarinic receptor is involved in CTL development, thus providing novel insights into CD8+ T cell biology and the potential role of cholinergic signaling in immune regulation.
Zimring
James C
JC
Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, Room 7301, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Kapp
Linda M
LM
Yamada
Masahisa
M
Wess
Jürgen
J
Kapp
Judith A
JA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D043643:Receptor, Muscarinic M1 / Q000172:deficiency / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000145:classification / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D017252:CD3 Complex; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D000109:Acetylcholine