Journal
JOURNAL OF IMMUNOLOGY
Volume 191, Issue 7, Pages 3705-3711Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300378
Keywords
-
Categories
Funding
- National Institute of Allergy and Infectious Diseases [1R21AI090150, 1R21AI092212, 1R21AI099825]
- National Heart, Lung, and Blood Institute Training Grant [T32 HL007910-14]
Ask authors/readers for more resources
The transcriptional repressor Bcl6 controls development of the follicular Th cell (T-FH) lineage, but the precise mechanisms by which Bcl6 regulates this process are unclear. A model has been proposed whereby Bcl6 represses the differentiation of T cells into alternative effector lineages, thus favoring T-FH cell differentiation. Analysis of T cell differentiation using Bcl6-deficient mice has been complicated by the strong proinflammatory phenotype of Bcl6-deficient myeloid cells. In this study, we report data from a novel mouse model where Bcl6 is conditionally deleted in T cells (Bcl6(fl/fl)Cre(CD4) mice). After immunization, programmed death-1 (PD-1)(high) T-FH cells in Bcl6(fl/fl)Cre(CD4) mice are decreased >90% compared with control mice, and Ag-specific IgG is sharply reduced. Residual PD-1(high)CXCR5(+) T-FH cells in Bcl6(fl/fl)Cre(CD4) mice show a significantly higher rate of apoptosis than do PD-1(high)CXCR5(+) T-FH cells in control mice. Immunization of Bcl6(fl/fl)Cre(CD4) mice did not reveal enhanced differentiation into Th1, Th2, or Th17 lineages, although IL-10 expression by CD4 T cells was markedly elevated. Thus, T cell-extrinsic factors appear to promote the increased Th1, Th2, and Th17 responses in germline Bcl6-deficient mice. Furthermore, IL-10 may be a key target gene for Bcl6 in CD4 T cells, which enables Bcl6 to promote the T-FH cell phenotype. Finally, our data reveal a novel mechanism for the role of Bcl6 in promoting T-FH cell survival.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available