T follicular helper, but not Th1, cell differentiation in the absence of conventional dendritic cells.
Development of long-lived humoral immunity is dependent on CXCR5-expressing T follicular helper (Tfh) cells, which develop concomitantly to effector Th cells that support cellular immunity. Conventional dendritic cells (cDCs) are critical APCs for initial priming of naive CD4(+) T cells but, importantly, also provide accessory signals that govern effector Th cell commitment. To define the accessory role of cDCs during the concurrent development of Tfh and effector Th1 cells, we performed high-dose Ag immunization in conjunction with the Th1-biased adjuvant polyinosinic:polycytidylic acid (pI:C). In the absence of cDCs, pI:C failed to induce Th1 cell commitment and IgG2c production. However, cDC depletion did not impair Tfh cell differentiation or germinal center formation, and long-lived IgG1 responses of unaltered affinity developed in mice lacking cDCs at the time point for immunization. Thus, cDCs are required for the pI:C-driven Th1 cell fate commitment but have no crucial accessory function in relation to Tfh cell differentiation.
Immunology Section, Lund University, 221 84 Lund, Sweden; and.
Madelene W
MW
Dahlgren
Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
Tobias
T
Gustafsson-Hedberg
Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
Megan
M
Livingston
Immunology Section, Lund University, 221 84 Lund, Sweden; and.
Helena
H
Cucak
Immunology Section, Lund University, 221 84 Lund, Sweden; and Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
Samuel
S
Alsén
Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden ulf.yrlid@gu.se bengt.johansson_lindbom@med.lu.se.
Ulf
U
Yrlid
Immunology Section, Lund University, 221 84 Lund, Sweden; and ulf.yrlid@gu.se bengt.johansson_lindbom@med.lu.se.
Bengt
B
Johansson-Lindbom
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002678:Chimera / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000276:immunology*; D054380:Receptors, CXCR5 / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*
C513179:CXCR5 protein, mouse; D007074:Immunoglobulin G; D054380:Receptors, CXCR5; D007371:Interferon-gamma; D011070:Poly I-C