Th2 activities induced during virgin T cell priming in the absence of IL-4, IL-13, and B cells.
Virgin T cells being primed to Th2-inducing or Th1-inducing Ags, respectively, start to synthesize IL-4 or IFN-gamma as they begin to proliferate. Parallel respective induction of B cells to produce gamma1 or gamma2a switch transcripts provides additional evidence of early divergent Th activity. This report concerns the roles of IL-4, IL-13, and B cells in these early events in vivo. Th2 responses were induced in lymph nodes against hapten-protein given s.c. with killed Bordetella pertussis adjuvant. In T cell proliferation in wild-type mice, IL-4 message up-regulation and gamma1 and epsilon switch transcript production were underway 48-72 h after immunization. The absence of IL-4, IL-13, or B cells did not alter the early T cell proliferative response. The gamma1 and epsilon switch transcript production was still induced in the absence of IL-4, IL-13, or both, but at a reduced level, while the dominance of switching to IgG1 in the extrafollicular hapten-specific plasma cell response was retained. The up-regulation of IL-4 message was not reduced or delayed in the absence of B cells and was only marginally reduced by the absence of IL-13. It is concluded that signals delivered by dendritic cells, which are not dependent on the presence of IL-4, IL-13, or B cells, can prime virgin T cells and induce the early Th2 activities studied. These early events that direct virgin T cells toward Th2 differentiation contrast with the critical later role of Th2 cytokines in selectively expanding Th2 clones and driving further IL-4 synthesis.
Cunningham
Adam F
AF
University of Birmingham, Medical Research Council Centre for Immune Regulation, Birmingham, United Kingdom.
Fallon
Padraic G
PG
Khan
Mahmood
M
Vacheron
Sonia
S
Acha-Orbea
Hans
H
MacLennan
Ian C M
IC
McKenzie
Andrew N
AN
Toellner
Kai-Michael
KM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002645:Chickens; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization / Q000379:methods; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007136:Immunoglobulins / Q000172:deficiency; D007279:Injections, Subcutaneous; D018793:Interleukin-13 / Q000172:deficiency* / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D008211:Lymphocyte Cooperation / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D005719:gamma-Globulins / Q000008:administration & dosage / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006241:Haptens; D007074:Immunoglobulin G; D007136:Immunoglobulins; D018793:Interleukin-13; D009596:Nitrophenols; D010648:Phenylacetates; D012333:RNA, Messenger; D005719:gamma-Globulins; C026242:4-hydroxy-5-nitrophenyl acetic acid; D015847:Interleukin-4