1. Giandor Saltz Gigley Molecuar Biology Lab INBRE Spring 2016
Define NK Cell Impact on Early CD8 T cell Responses to Toxoplasma gondii Infection
Giandor Saltz
Gigley Molecuar Biology Lab
INBRE Spring 2016

2. Outline The Immune System and NK Cells
Role of NK cells in viral infections
Chronic Infections and Immune Exhaustion
T. gondii
Research Question
Experimental Procedure
Results
Conclusion
Questions

3. The Immune System

4. Natural Killer Cells Functions:
Detection of stressed or non-self cells
Cytotoxic
Cytokine production
University of Minnesota, 2016

5. Chronic Infection
Chronic Infection – Immune system controls infection, but cannot clear it completely
90% of population has a chronic infection
Susceptible to chronic infection reactivation: Immunosuppressed groups: HIV/AIDS, Cancer patients, Organ transplant patients, Autoimmune disease

6. Why do we get Chronic Infections?
Immune Exhaustion – Immune System still functional, but tired
CD8 T cells important for long term control, affected by immune exhaustion
Reasons for developing immune exhaustion are unknown

7. Role of NK cells in Immune Exhaustion
NK cells important in control of acute infections
Role of NK cells in infection is more complex than originally thought – implicated in immune exhaustion
Viral Infections
Early depletion of NK cells in persistent viral infections is therapeutic (Waggoner et al, 2014)

8. Toxoplasma gondii
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved
Photo: D. Ferguson, Oxford University)

9. Research Question
What happens to the CD8 T cell response to T. gondii when you eliminate NK cells early in infection?

10. Experimental Procedure
3 groups of mice: Naïve, Parasite Infected, Parasite Infected/NK depleted
4 males in each group 6 weeks of age
Infected with 10 cysts
Depleted NK cells Days -1, 0, 3, and 5 (Antibody PK136)
Harvested spleens Day 7
Analyze CD8 T cell response (IFNγ production) by Flow Cytometry

11. Results Naive D7 ME49 NK- D7 ME49 CD8 IFN-gamma Frequency
Absolute Number
Absolute # IFNg+
CD8 T cells X 10^5
% CD8 T cells IFNg+

12. Conclusions
What happens to the CD8 T cell response to T. gondii when you eliminate NK cells early in infection?
Viral model: Eliminating NK cells early in infection improves CD8 T cell response
T. gondii: Eliminating NK cells early in infection decreases CD8 T cell response

13. Thank you! Funding: INBRE Spring 2016
Dr. Jason Gigley and Lab Members:
Daria Ivanova
Steve Denton
David Stevenson
David Rach
Kevin Fettel
Dominic Cancino
Rida Fatima

14. Audience Questions