A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8(+) T cell responses to rabies virus

粒细胞-巨噬细胞集落刺激因子在调节狂犬病毒 CD8(+) T 细胞应答中的作用

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作者:Celestine N Wanjalla, Elizabeth F Goldstein, Christoph Wirblich, Matthias J Schnell

Abstract

Inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. Here, we analyzed the effect of GM-CSF on a RABV-vaccine vector co-expressing HIV-1 Gag. To this end, we immunized mice with RABV expressing HIV-1 Gag and GM-CSF and analyzed the primary and recall CD8(+) T cell responses. We observed a statistically significant increase in antigen presenting cells (APCs) in the spleen and draining lymph nodes in response to GM-CSF. Despite the increase in APCs, the primary and memory anti HIV-1 CD8(+) T cell response was significantly lower. This was partly likely due to lower levels of proliferation in the spleen. Animals treated with GM-CSF neutralizing antibodies restored the CD8(+) T cell response. These data define a role of GM-CSF expression, in the regulation of the CD8(+) T cell immune responses against RABV and has implications in the use of GM-CSF as a molecular adjuvant in vaccine development.

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