Whole body irradiation impairs naïve CD4 T cell function

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B730
Abstract ID: 4680

Presenting Author:
Shravan Kumar Kannan , Graduate Student at Univ. of Iowa

Abstract:

Advancements in nuclear power and radiotherapy have expanded new avenues for whole-body irradiation (WBI) to humans, urging the need to understand its impact on immune cells. While most studies focus on the numerical recovery of naïve T cells post-WBI, less is known regarding its impact on their function. We subjected B6 SPF mice to 0/5Gy doses of WBI and used I-A^b tetramer enrichment to track the recovery of naïve CD4s of different antigen specificities post WBI. The number of MOG₄₀ specific CD4 T cells is diminished 10 days post-irradiation (DPR), and recovered by 40DPR. To test if they are able to induce EAE post-WBI, we administered MOG+CFA, followed by pertussis toxin (PTX). The 10DPR mice showed delayed EAE development, likely due to diminished MOG₄₀ naïve precursors. Interestingly, the 40DPR mice potentiated EAE compared to the 0Gy mice, evidenced by increased CD4 priming in the dLN, and spine infiltration. While WBI-mediated CD4 T cell-intrinsic changes could contribute to the timing/severity of EAE, T cell-extrinsic factors could also influence disease. To test if WBI compromises the blood-brain barrier (BBB) and facilitates EAE progression, EAE is induced in +/-WBI mice without PTX. In the absence of PTX, 0Gy mice did not develop EAE, while the 10- and 40DPR mice developed EAE suggesting BBB impairment. Overall, WBI directly impacts the number and function of autoreactive CD4 T cells, while helping them enter the spine by changing the environment.