Selective effects of NF-κB1 deficiency in CD4 T cells on Th2 and TFh induction by alum-precipitated protein vaccines.

TY - JOUR

T1 - Selective effects of NF-κB1 deficiency in CD4 T cells on Th2 and TFh induction by alum-precipitated protein vaccines.

AU - Serre, Karine

AU - Mohr, E

AU - Benezech, Cecile

AU - Bird, Roger

AU - Khan, MA

AU - Caamaño, JH

AU - Cunningham, Adam

AU - MacLennan, Ian

PY - 2011/4/6

Y1 - 2011/4/6

N2 - NF-κB1-dependent signaling directs the development of CD4 Th2 cells during allergic airways inflammation and protective responses to helminth infection. Here, we show that IL-4 and IL-13 production is NF-κB1-dependent in mouse ovalbumin-specific CD4 (OTII) T cells responding to alum-precipitated ovalbumin (alumOVA) immunization. More surprisingly, we found that NF-κB1-deficiency in OTII cells also selectively impairs CXCR5 induction by alumOVA without affecting upregulation of BCL6, IL-21, OX40 and CXCR4 mRNA and PD-1 protein. This results in functional impairment of follicular helper T (TFh) cells. Thus, fewer germinal center B cells develop in lymph node responses to alumOVA in T-cell-deficient mice reconstituted with NF-κB1OTII cells as opposed to NF-κB1(+/+) OTII cells, while plasma cell numbers are comparable. Unlike CXCR5 induction in CD4 T cells, NF-κB1-deficient recirculating follicular B cells are shown to express normal levels of CXCR5. The selective effects of NF-κB1-deficiency on Th2 and TFh induction does not appear to be due to altered expression of the Th2-associated transcription factors - GATA-3, c-Maf and Ikaros. Altogether, these results suggest that NF-κB1 regulates the expression of CXCR5 on CD4 T cells primed in vivo, and thus selectively controls the T-cell-dependent germinal center component of B-cell response to alumOVA.

AB - NF-κB1-dependent signaling directs the development of CD4 Th2 cells during allergic airways inflammation and protective responses to helminth infection. Here, we show that IL-4 and IL-13 production is NF-κB1-dependent in mouse ovalbumin-specific CD4 (OTII) T cells responding to alum-precipitated ovalbumin (alumOVA) immunization. More surprisingly, we found that NF-κB1-deficiency in OTII cells also selectively impairs CXCR5 induction by alumOVA without affecting upregulation of BCL6, IL-21, OX40 and CXCR4 mRNA and PD-1 protein. This results in functional impairment of follicular helper T (TFh) cells. Thus, fewer germinal center B cells develop in lymph node responses to alumOVA in T-cell-deficient mice reconstituted with NF-κB1OTII cells as opposed to NF-κB1(+/+) OTII cells, while plasma cell numbers are comparable. Unlike CXCR5 induction in CD4 T cells, NF-κB1-deficient recirculating follicular B cells are shown to express normal levels of CXCR5. The selective effects of NF-κB1-deficiency on Th2 and TFh induction does not appear to be due to altered expression of the Th2-associated transcription factors - GATA-3, c-Maf and Ikaros. Altogether, these results suggest that NF-κB1 regulates the expression of CXCR5 on CD4 T cells primed in vivo, and thus selectively controls the T-cell-dependent germinal center component of B-cell response to alumOVA.

U2 - 10.1002/eji.201041126

DO - 10.1002/eji.201041126

M3 - Article

C2 - 21469117

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

ER -