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Regulation of CD4+ T-Cell Function by Membrane Cholesterol

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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The CD4 T helper cells play a central role in initiating immune responses to various types of infections that have breached the immune defense. In the context of vaccination, CD4 T-cells are critical for establishing broad, long-lasting protective immunity. It is known that T-regulatory cells T-regs can limit CD4 T-cell responses during influenza viral infection, however less is known about the effect of T-regs in influenza vaccination. In this dissertation, I first present evidence that the size of CD4Foxp3 T-reg pool is an important modulatory component of the primary and memory T-cell responses to influenza vaccination. Herein, I found that immunization of BALBc mice with a prototype of influenza APR834 virus vaccine expanded the CD4Foxp3 T-reg pool and fostered the development of virus-specific CD4Foxp3 T-reg cells. Increasing the size of Foxp3 T-reg pool did not alter the primary PR8-specific B-cell response, but it did suppress the primary and memory PR8-specific T helper responses induced by vaccination. In contrast, the vaccination-induced T helper cell response was augmented when the pool of CD4Foxp3 T-regs was decreased by 50.

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