Rescue of Vaccine T cell Memory Following Sublethal Gamma Irradiation

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	FDA/CBER	IMMUNO-2

* FARE Award Winner

Authors

• J.D. Berkson
• H.I. McFarland
• J. Lee
• A. Elkahloun
• A.S. Rosenberg

Abstract

Subsequent to sublethal γ radiation exposure, survivors reacquire immune competence, but lose vaccine immunity. Our goal is to rescue CD8+ T cell-mediated memory responses following γ radiation exposure. In a mouse model of Listeria monocytogenes (LM) infection, we found that sub lethally irradiated mice succumb to infection with an attenuated strain of Listeria, LM-ActA, when revaccinated at 3 days or more post-irradiation (PI), but survive if revaccinated at 0-2 days PI. A signature of rescue was revealed in gene profiling studies in which a group of cytokines and chemokines were uniquely up regulated in the spleens of LM-rescued animals. These included factors important in resistance to LM, such as proinflammatory factors, CCL2, TNFα, IL-6, and bacterocidal factors CXCL9, 10, and 11 as well as anti-apoptotic factors including IL-15 and IER3 which may have a role in rescue of memory CTL. RAW264.7, a macrophage cell line, produced a similar cytokine profile when irradiated and infected with LM, suggesting a probable myeloid source for the majority of these factors. Monocyte activation by the combination of irradiation and LM infection may thus create conditions of rescue by producing cytokines and chemokines that enhance clearance of LM and rescue CD8+ CTL mediating vaccine immunity.

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