T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine.
CD73 (5'-ectonucleotidase) is expressed by two distinct mouse CD4 T cell populations: CD25+ (FoxP3+) T regulatory (Treg) cells that suppress T cell proliferation but do not secrete IL-2, and CD25- uncommitted primed precursor Th (Thpp) cells that secrete IL-2 but do not suppress in standard Treg suppressor assays. CD73 on both Treg and Thpp cells converted extracellular 5'-AMP to adenosine. Adenosine suppressed proliferation and cytokine secretion of Th1 and Th2 effector cells, even when target cells were activated by anti-CD3 and anti-CD28. This represents an additional suppressive mechanism of Treg cells and a previously unrecognized suppressive activity of Thpp cells. Infiltration of either Treg or Thpp cells at inflammatory sites could potentially convert 5'-AMP generated by neutrophils or dying cells into the anti-inflammatory mediator adenosine, thus dampening excessive immune reactions.
Kobie
James J
JJ
David H. Smith Center for Vaccine Biology and Immunology and Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Shah
Pranav R
PR
Yang
Li
L
Rebhahn
Jonathan A
JA
Fowell
Deborah J
DJ
Mosmann
Tim R
TR
D015720:5'-Nucleotidase / Q000096:biosynthesis / Q000502:physiology*; D000241:Adenosine / Q000378:metabolism* / Q000502:physiology; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006825:Hybridomas; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D006131:Growth Inhibitors; D018836:Inflammation Mediators; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D000241:Adenosine