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Why this Project?
T helper cells are essential for generating effective immune defenses against tumors, virus-infection and elimination of other aberrant cells. This project will investigate the mechanisms that control the balance of T helper lymphocytesubsets under conditions of low dose, low-LET radiation exposure.
Project Goals:
- To determine whether whole-body exposure to either low dose photons ( g -rays) will alter the level of IFN- g secretion, which may inhibit T-helper cell function.
- To quantify low dose photon effects on T helper lymphocyte gene expression and signal transduction pathways.
- To determine if exposure to low dose proton radiation will induce a change in the types and number of cell subsets compared to similar doses of photons.
Experimental Approach:
- C57BL/6 mice will be exposed (~ 0.03cGy/hr) to 60Co g -rays to total doses of 0, 0.01, 0.05 and 0.1 Gy. Spleens from a subset per group will be evaluated for T helper cell gene expression patterns immediately after irradiation (day 0, i.e. within 1-2 hr) using microarrays designed specifically for T helper cell biology.
- Spleens from the remaining mice will be assessed for the number of T helper 1, T helper 2, and T helper 3 cells based on intracellular cytokines and levels of secreted cytokines on days 0, 4, 20 and 40 post-exposure.
- The same protocols and assays will be performed at the same time points utilizing low dose proton radiation. This will demonstrate whether low-LET radiations (protons or photons), with different track structures, affect T helper cells similarly or differently.
Expected Outcomes:
- Collectively, the data should provide new information on the underlying mechanisms by which low dose, low-LET radiations influence the interactive balance among the T helper 1, T helper 2, and T helper 3 cell subsets. Depression or dysfunctional interaction among these T cell populations can lead to increased risk for cancer, infectious diseases, allergy and a number of other pathological conditions.
- The results should also identify productive avenues for countermeasure development.
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