These studies investigate factors involved in differentiation, maintenance, and trafficking of T and B lymphocytes. Homeostasis of naive CD8 T cells relies on encounter with self MHC molecules. Previous work from our group and others indicate that T cells deprived of such cues change in their phenotype and exhibit Impaired survival: yet cells showing features of poor homeostasis are present at steady state in normal animals.
In Aim 1, we investigate how such cells are maintained, and whether they play a distinct role in the response to foreign antigen.
In Aims 2 and 3, we explore the function of the transcription factor KLF2 in T and B cells. Our preliminary data detected unexpected heterogeneity of KLF2 expression among certain subsets of memory CD4 and CDS T cells. Given KLF2's role in T cell trafficking and potentially in ceil quiescence, we will investigate the significance of KLF2 regulation on memory T cell subset localization and function. Lastly, in Aim 3, we build on surprising preliminary data indicating KLF2 is required for normal development of B cell subsets and is important for B cell functional responses. These studies will explore the impact of KLF2 in directing B cell differentiation and survival, as well as investigate the functional relevance of KLF2 regulated genes in B cell activation.

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National Institute of Health (NIH)
Method to Extend Research in Time (MERIT) Award (R37)
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No Study Section (in-house review) (NSS)
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Lapham, Cheryl K
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University of Minnesota Twin Cities
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Hogquist, Kristin A; Jameson, Stephen C (2014) The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function. Nat Immunol 15:815-23
Olson, Janelle A; McDonald-Hyman, Cameron; Jameson, Stephen C et al. (2013) Effector-like CD8? T cells in the memory population mediate potent protective immunity. Immunity 38:1250-60
Skon, Cara N; Lee, June-Yong; Anderson, Kristin G et al. (2013) Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells. Nat Immunol 14:1285-93
Hamilton, Sara E; Jameson, Stephen C (2012) CD8 T cell quiescence revisited. Trends Immunol 33:224-30
Akue, Adovi D; Lee, June-Yong; Jameson, Stephen C (2012) Derivation and maintenance of virtual memory CD8 T cells. J Immunol 188:2516-23
Hart, Geoffrey T; Hogquist, Kristin A; Jameson, Stephen C (2012) Kruppel-like factors in lymphocyte biology. J Immunol 188:521-6
Takada, Kensuke; Wang, Xiaodan; Hart, Geoffrey T et al. (2011) Kruppel-like factor 2 is required for trafficking but not quiescence in postactivated T cells. J Immunol 186:775-83
Hart, Geoffrey T; Wang, Xiaodan; Hogquist, Kristin A et al. (2011) Kruppel-like factor 2 (KLF2) regulates B-cell reactivity, subset differentiation, and trafficking molecule expression. Proc Natl Acad Sci U S A 108:716-21
Weinreich, Michael A; Odumade, Oludare A; Jameson, Stephen C et al. (2010) T cells expressing the transcription factor PLZF regulate the development of memory-like CD8+ T cells. Nat Immunol 11:709-16
Johnson, Lisa D S; Jameson, Stephen C (2010) Self-specific CD8+ T cells maintain a semi-naive state following lymphopenia-induced proliferation. J Immunol 184:5604-11

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