Memory CD8+ T cells provide essential specific immunity against previously encountered antigens, and formation of such cells is a fundamental goal of vaccination. Our data show that the pre-immune population of CD8 T cells contains cells with memory-like properties, which we call "Homeostatic memory" (HM) cells. In this proposal we will test how this population of T cells contributes to primary immune responses. Building on our previous data, we will conduct two aims. 1) how the HM pool responds to pathogens early during an immune response, and how these cells may affect pathogen growth or immunopathology that can arise during immune responses. We will also extend data suggesting HM cells differ qualitatively from "na?ve" cells in their response to antigen. 2) This aim extends preliminary data suggesting the cytokine IL-4 plays an unexpected role in controlling CD8 T cell responses. We will assess the function of IL- 4 in controlling memory CD8 T cell maintenance, and build on our preliminary data showing that IL-4 supports the CD8 response to pathogens, by determining the stage at which IL-4 mediates its effects.

Public Health Relevance

T cells make up a key part of the immune system, helping to eliminate infections. Vaccines are designed to make memory T cells which remember microbial components and so stop pathogens (damaging infectious agents) early after an infection. Our research has shown that there are memory T cells specific for pathogens present in the immune system even before an animal has been vaccinated - we wish to understand how these cells may offer natural immunity, giving a measure of resistance to pathogens one has never encountered before, and also how these pre-existing memory cells may enhance immune memory after infection.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AI075168-07
Application #
8660594
Study Section
Immunity and Host Defense (IHD)
Program Officer
Kelly, Halonna R
Project Start
Project End
Budget Start
Budget End
Support Year
7
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
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
Lee, You Jeong; Holzapfel, Keli L; Zhu, Jinfang et al. (2013) Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells. Nat Immunol 14:1146-54
Akue, Adovi D; Lee, June-Yong; Jameson, Stephen C (2012) Derivation and maintenance of virtual memory CD8 T cells. J Immunol 188:2516-23
Hamilton, Sara E; Jameson, Stephen C (2012) CD8 T cell quiescence revisited. Trends Immunol 33:224-30
Jameson, Stephen C; Masopust, David (2009) Diversity in T cell memory: an embarrassment of riches. Immunity 31:859-71