title: Early simultaneous production of intranodal CD4 Th2 effectors and recirculating rapidly responding central-memory-like CD4 T cells.
abstract: This study characterizes the diversity of CD4 Th cells produced during a Th2 response in vivo. Kinetics of effector and memory cell differentiation by mouse OVA-specific CD4 T cells was followed during primary responses to alum-precipitated OVA. The complexity of the CD4 T response was assessed in nodes draining and distant from the site of immunization for phenotype, location and function. By 3 days IL-4-producing effector CD4 T cells developed in the draining node and a proportion of the responding cells had migrated to B-cell follicles, while yet others had left the draining node. Some of these early migrant cells were recirculating cells with a central memory phenotype. These had divided four or more times in the draining node before migrating to distant nodes not exposed to antigen. We questioned the responsiveness of these early central-memory-like cells on secondary antigen challenge at sites distant to the primary immunization. They re-entered cell cycle and migrated to B-cell follicles, much more rapidly than naive CD4 T cells and could still be induced to produce IL-4. Their production and survival were independent of the starting frequency of antigen-specific CD4 T cells. Thus intranodal effector cells and recirculating, rapidly responding central-memory-like cells emerged simultaneously from the third day of a primary Th2 response.
authors.affiliation: MRC Centre for Immune Regulation, the IBR, Department of Immunology, University of Birmingham, Birmingham, UK. k.serre@bham.ac.uk
authors.forename: Karine
authors.initials: K
authors.lastname: Serre
authors.forename: Elodie
authors.initials: E
authors.lastname: Mohr
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Roger
authors.initials: R
authors.lastname: Bird
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D015870:Gene Expression / Q000276:immunology; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D054380:Receptors, CXCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D018183:Transplantation Chimera / Q000276:immunology; D014611:Vaccination
chemical_list: D015703:Antigens, CD; C513179:CXCR5 protein, mouse; D011948:Receptors, Antigen, T-Cell; D054380:Receptors, CXCR5; D015847:Interleukin-4; D010047:Ovalbumin; D017493:Leukocyte Common Antigens