The cytokine IL-4 is well studied for its role in driving allergic/asthmatic CD4 T cell responses: However its impact on CD8 T cells is much less clear. Building on published and preliminary data, we propose that IL-4 plays a critical and unexpected role in supporting the CD8 T cell response to pathogens. These findings will be investigated further to define the exact role of IL-4 responsiveness in the CD8 T cell response, and additional work will test the novel concept that IL-4 cytokine therapy could be used to enhance CD8 T cell protective immunity against malarial parasites.

Public Health Relevance

Many infections are controlled by """"""""killer"""""""" T lymphocytes (CTL), and there is a pressing need to improve vaccines that produce these cells. Here we look at an unexpected and interesting role for a serum protein called IL-4 which, based on our preliminary data, is critical to achieve a strong CTL response against infection. We test the role of IL-4 in the CTL responses against two pathogens (Listeria bacteria and malaria parasites) to establish what IL-4 does in controlling CTL responses (Aim 1) and test how this protein can be used to enhance CTL activity in order to prevent malarial disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI100088-01
Application #
8293998
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Lapham, Cheryl K
Project Start
2012-02-15
Project End
2014-01-31
Budget Start
2012-02-15
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$228,000
Indirect Cost
$78,000
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Burrack, Kristina S; Huggins, Matthew A; Taras, Emily et al. (2018) Interleukin-15 Complex Treatment Protects Mice from Cerebral Malaria by Inducing Interleukin-10-Producing Natural Killer Cells. Immunity 48:760-772.e4
Renkema, Kristin R; Lee, June-Yong; Lee, You Jeong et al. (2016) IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection. J Exp Med 213:1319-29