TY - JOUR
T1 - BCL6b mediates the enhanced magnitude of the secondary response of memory CD8 T lymphocytes
AU - Manders, P.M.
AU - Hunter, P.J.
AU - Telaranta, A.I.
AU - Carr, J.M.
AU - Marshall, J.L.
AU - Carrasco, M.
AU - Murakami, Y.
AU - Fearon, D.T.
AU - Palmowski, M.J.
AU - Cerundolo, V.
AU - Kaech, S.M.
AU - Ahmed, R.
PY - 2005/5/24
Y1 - 2005/5/24
N2 - A characteristic of the secondary response of CD8 T cells that distinguishes it from the primary response is the generation of greater numbers of effector cells. Because effector CD8 T cells are derived from a pool of less differentiated, replicating cells in secondary lymphoid organs, and because IL-2 mediates effector differentiation, the enhanced secondary response may reflect the enlargement of this generative pool by the transient repression of IL-2-mediated differentiation. We have examined for this function the transcriptional represser BCL6b, a homologue of BCL6 that represses IL-2-induced B cell differentiation. BCL6b is expressed in a small subset of antigen-experienced CD8 T cells. Ectopic expression of BCL6b in CD8 T cells diminishes their growth in response to IL-2 in vitro. Female mice in which the BCL6b gene has been interrupted have normal primary responses of CD8 T cells to infection with vaccinia expressing the H-Y epitope, Uty, but Uty-specific, BCL6b , memory CD8 T cells have diminished recall proliferative responses to this epitope in vitro. BCL6b mice also have normal primary CD8 T cell responses to influenza infection, but nucleoprotein peptide-specific, BCL6b , memory CD8 T cells have a cell autonomous defect in the number of effector cells generated in response to reinfection. Therefore, BCL6b is required for the enhanced magnitude of the secondary response of memory CD8 T cells.
AB - A characteristic of the secondary response of CD8 T cells that distinguishes it from the primary response is the generation of greater numbers of effector cells. Because effector CD8 T cells are derived from a pool of less differentiated, replicating cells in secondary lymphoid organs, and because IL-2 mediates effector differentiation, the enhanced secondary response may reflect the enlargement of this generative pool by the transient repression of IL-2-mediated differentiation. We have examined for this function the transcriptional represser BCL6b, a homologue of BCL6 that represses IL-2-induced B cell differentiation. BCL6b is expressed in a small subset of antigen-experienced CD8 T cells. Ectopic expression of BCL6b in CD8 T cells diminishes their growth in response to IL-2 in vitro. Female mice in which the BCL6b gene has been interrupted have normal primary responses of CD8 T cells to infection with vaccinia expressing the H-Y epitope, Uty, but Uty-specific, BCL6b , memory CD8 T cells have diminished recall proliferative responses to this epitope in vitro. BCL6b mice also have normal primary CD8 T cell responses to influenza infection, but nucleoprotein peptide-specific, BCL6b , memory CD8 T cells have a cell autonomous defect in the number of effector cells generated in response to reinfection. Therefore, BCL6b is required for the enhanced magnitude of the secondary response of memory CD8 T cells.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-21144449046&md5=d9dc0ea678e1924bbceaface489872c3
U2 - 10.1073/pnas.0501585102
DO - 10.1073/pnas.0501585102
M3 - Article
AN - SCOPUS:21144449046
SN - 0027-8424
VL - 102
SP - 7418
EP - 7425
JO - National Academy of Sciences. Proceedings
JF - National Academy of Sciences. Proceedings
IS - 21
ER -