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.
|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|
|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 42:252-264|
|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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