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)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI038903-17
Application #
8279149
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lapham, Cheryl K
Project Start
1996-07-01
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
17
Fiscal Year
2012
Total Cost
$369,882
Indirect Cost
$119,882
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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

Showing the most recent 10 out of 16 publications