BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes.

Journal article

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 repressor 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.

Authors: Manders, P; Hunter, P; Telaranta, A; Carr, J; Marshall, J

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 102
• Issue: 21
• Pages: 7418-7425
• Publication date: 2005-05-01
• DOI: 10.1073/pnas.0501585102
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Gene Targeting; Gene Components; Female; H-Y Antigen; Repressor Proteins; Immunologic Memory; Silencer Elements, Transcriptional; Mice, Knockout; CD8-Positive T-Lymphocytes; Epitopes; Interferon-gamma; Genetic Vectors; Cell Differentiation; Vaccinia; Reverse Transcriptase Polymerase Chain Reaction; Mice; Interleukin-2; DNA Primers; Moloney murine leukemia virus; Humans; Animals