Giuseppe
Emeritus
IFN-γ produced by CD8 T cells induces T-bet?dependent and ?independent class switching in B cells in responses to alum-precipitated protein vaccine (PNAS, abstract, edited)
[Source: PNAS, <cite cite="http://www.pnas.org/content/107/40/17292.short?rss=1">IFN-γ produced by CD8 T cells induces T-bet?dependent and ?independent class switching in B cells in responses to alum-precipitated protein vaccine ? PNAS</cite>. Full text, . Abstract, edited.]
IFN-γ produced by CD8 T cells induces T-bet?dependent and ?independent class switching in B cells in responses to alum-precipitated protein vaccine
1. Elodie Mohr 1, 2. Adam F. Cunningham, 3. Kai-Michael Toellner, 4. Saeeda Bobat, 5. Ruth E. Coughlan, 6. Roger A. Bird, 7. Ian C. M. MacLennan, and 8. Karine Serre 1
Author Affiliations
1. Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
1. Edited by Antony Basten, Garvan Institute, Darlinghurst, Sydney, NSW, Australia, and accepted by the Editorial Board August 27, 2010 (received for review April 15, 2010)
Abstract
Alum-precipitated protein (alum protein) vaccines elicit long-lasting neutralizing antibody responses that prevent bacterial exotoxins and viruses from entering cells. Typically, these vaccines induce CD4 T cells to become T helper 2 (Th2) cells that induce Ig class switching to IgG1. We now report that CD8 T cells also respond to alum proteins, proliferating extensively and producing IFN-γ, a key Th1 cytokine. These findings led us to question whether adoptive transfer of antigen-specific CD8 T cells alters the characteristic CD4 Th2 response to alum proteins and the switching pattern in responding B cells. To this end, WT mice given transgenic ovalbumin (OVA)-specific CD4 (OTII) or CD8 (OTI) T cells, or both, were immunized with alum-precipitated OVA. Cotransfer of antigen-specific CD8 T cells skewed switching patterns in responding B cells from IgG1 to IgG2a and IgG2b. Blocking with anti?IFN-γ antibody largely inhibited this altered B-cell switching pattern. The transcription factor T-bet is required in B cells for IFN-γ?dependent switching to IgG2a. By contrast, we show that this transcription factor is dispensable in B cells both for IFN-γ?induced switching to IgG2b and for inhibition of switching to IgG1. Thus, T-bet dependence identifies distinct transcriptional pathways in B cells that regulate IFN-γ?induced switching to different IgG isotypes.
* B-cell Ig class switch
* T helper 1 cells
* T helper 2 cells
* IgG2a
* IgG2b
Footnotes
* 1 To whom correspondence may be addressed. E-mail: emohr@igc.gulbenkian.pt or karine@kserre.net.
* Author contributions: E.M., A.F.C., I.C.M.M., and K.S. designed research; E.M., S.B., R.E.C., and K.S. performed research; K.-M.T. and R.A.B. contributed new reagents/analytic tools; E.M., I.C.M.M., and K.S. analyzed data; and E.M., I.C.M.M., and K.S. wrote the paper.
* The authors declare no conflict of interest.
* This article is a PNAS Direct Submission. A.B. is a guest editor invited by the Editorial Board.
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1004879107/-/DCSupplemental.
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[Source: PNAS, <cite cite="http://www.pnas.org/content/107/40/17292.short?rss=1">IFN-γ produced by CD8 T cells induces T-bet?dependent and ?independent class switching in B cells in responses to alum-precipitated protein vaccine ? PNAS</cite>. Full text, . Abstract, edited.]
IFN-γ produced by CD8 T cells induces T-bet?dependent and ?independent class switching in B cells in responses to alum-precipitated protein vaccine
1. Elodie Mohr 1, 2. Adam F. Cunningham, 3. Kai-Michael Toellner, 4. Saeeda Bobat, 5. Ruth E. Coughlan, 6. Roger A. Bird, 7. Ian C. M. MacLennan, and 8. Karine Serre 1
Author Affiliations
1. Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
1. Edited by Antony Basten, Garvan Institute, Darlinghurst, Sydney, NSW, Australia, and accepted by the Editorial Board August 27, 2010 (received for review April 15, 2010)
Abstract
Alum-precipitated protein (alum protein) vaccines elicit long-lasting neutralizing antibody responses that prevent bacterial exotoxins and viruses from entering cells. Typically, these vaccines induce CD4 T cells to become T helper 2 (Th2) cells that induce Ig class switching to IgG1. We now report that CD8 T cells also respond to alum proteins, proliferating extensively and producing IFN-γ, a key Th1 cytokine. These findings led us to question whether adoptive transfer of antigen-specific CD8 T cells alters the characteristic CD4 Th2 response to alum proteins and the switching pattern in responding B cells. To this end, WT mice given transgenic ovalbumin (OVA)-specific CD4 (OTII) or CD8 (OTI) T cells, or both, were immunized with alum-precipitated OVA. Cotransfer of antigen-specific CD8 T cells skewed switching patterns in responding B cells from IgG1 to IgG2a and IgG2b. Blocking with anti?IFN-γ antibody largely inhibited this altered B-cell switching pattern. The transcription factor T-bet is required in B cells for IFN-γ?dependent switching to IgG2a. By contrast, we show that this transcription factor is dispensable in B cells both for IFN-γ?induced switching to IgG2b and for inhibition of switching to IgG1. Thus, T-bet dependence identifies distinct transcriptional pathways in B cells that regulate IFN-γ?induced switching to different IgG isotypes.
* B-cell Ig class switch
* T helper 1 cells
* T helper 2 cells
* IgG2a
* IgG2b
Footnotes
* 1 To whom correspondence may be addressed. E-mail: emohr@igc.gulbenkian.pt or karine@kserre.net.
* Author contributions: E.M., A.F.C., I.C.M.M., and K.S. designed research; E.M., S.B., R.E.C., and K.S. performed research; K.-M.T. and R.A.B. contributed new reagents/analytic tools; E.M., I.C.M.M., and K.S. analyzed data; and E.M., I.C.M.M., and K.S. wrote the paper.
* The authors declare no conflict of interest.
* This article is a PNAS Direct Submission. A.B. is a guest editor invited by the Editorial Board.
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1004879107/-/DCSupplemental.
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