Pou6f1 is dispensable for mouse T cell development and virus-specific memory CD8+ T cell generation
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1
Brigham and Women’s Hospital, Harvard Medical School, Department of Pathology, United States
Pou6f1 is a POU-domain transcription factor whose paralogs control self-renewal (e.g. Oct-4) and cell fate determination (e.g. Pit-1, Brn3a). It has been shown to be selectively upregulated at the DN3a to DP stages in thymocytes; and across different models in antigen-specific memory/memory-precursors relative to shorter-lived mature CD8+ T lymphocytes. On these bases, we hypothesized that it is required for maintaining a multipotent and/or differentiation-poised state in T cells. To test this, we quantitatively validated its differential expression in lymphocytes, and generated and characterized conditional (Cre/loxP-based) Pou6f1 knockout mice. Germ-line deletion (EIIa-Cre-driven) resulted in viable and fertile progeny with no obvious morphological or behavioral abnormalities. Mice with an early deletion in thymocytes (Lck-Cre-driven) showed normal numbers and phenotype of thymic populations (DN, DP, SP4 and SP8) and peripheral CD4+ and CD8+ T cells, according to the expression of TCRβ, CD3, and activation (CD5, CD44, CD69), differentiation (CD25, CD27, CD28, CD62L, CD122), survival (CD127) and senescence (Klrg1) markers. Likewise, specific deletion in CD8+ cells (E8I/CD8a-Cre-driven) did not affect either antigen-specific CD8+ T cell effector response (ex-vivo OVA-induced IFN-γ synthesis), or memory generation (pentamer binder frequency) and response upon infection with vaccinia-OVA virus. The effects on both memory formation in a competitive adoptive transfer setting and secondary responses are under study. In conclusion, this is the first description of a Pou6f1 knockout mouse. Results to date suggest that Pou6f1 may not be involved in lineage commitment of thymocytes or CD8+ T lymphocytes, or that in the current experimental models its loss is compensated.
Keywords:
Pou6f1,
CD8+ T cell memory,
T cell development,
POU-domain transcription factor,
conditional knockout
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Carrasco-Alfonso
MJ,
Jiang
W and
Luckey
J
(2013). Pou6f1 is dispensable for mouse T cell development and virus-specific memory CD8+ T cell generation.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01013
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Received:
30 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Marlene J Carrasco-Alfonso, Brigham and Women’s Hospital, Harvard Medical School, Department of Pathology, Boston, MA, 02115, United States, marleneca@hotmail.com
Dr. John Luckey, Brigham and Women’s Hospital, Harvard Medical School, Department of Pathology, Boston, MA, 02115, United States, cluckey@partners.org