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.

Public Health Relevance

Agency
National Institute of Health (NIH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI038903-19
Application #
8683059
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Lapham, Cheryl K
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Fulton, Ross B; Hamilton, Sara E; Xing, Yan et al. (2015) The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8(+) T cells to respond to foreign antigens. Nat Immunol 16:107-17
Lee, June-Yong; Skon, Cara N; Lee, You Jeong et al. (2015) The transcription factor KLF2 restrains CD4⁺ T follicular helper cell differentiation. Immunity 42:252-64
Takada, Kensuke; Van Laethem, Francois; Xing, Yan et al. (2015) TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells. Nat Immunol 16:1069-76
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
Shi, Hong; Sheng, Baiyang; Zhang, Feng et al. (2013) Kruppel-like factor 2 protects against ischemic stroke by regulating endothelial blood brain barrier function. Am J Physiol Heart Circ Physiol 304:H796-805
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
Akue, Adovi D; Lee, June-Yong; Jameson, Stephen C (2012) Derivation and maintenance of virtual memory CD8 T cells. J Immunol 188:2516-23
Lee, June-Yong; Jameson, Stephen C (2012) Immunology. Remembering to be tolerant. Science 335:667-8
Johnson, Lisa D S; Jameson, Stephen C (2012) TGF-ýý sensitivity restrains CD8+ T cell homeostatic proliferation by enforcing sensitivity to IL-7 and IL-15. PLoS One 7:e42268

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