Obuku Andrew Ekii, Bugembe Daniel L, Musinguzi Kenneth, Watera Christine, Serwanga Jennifer, Ndembi Nicaise, Levin Jonathan, Kaleebu Pontiano, Pala Pietro
Medical Research Council/Uganda Virus Research Institute , Uganda Research Unit on AIDS, Entebbe, Uganda .
AIDS Res Hum Retroviruses. 2016 Mar;32(3):237-46. doi: 10.1089/AID.2015.0157. Epub 2015 Dec 9.
Control of HIV replication through CD4(+) and CD8(+) T cells might be possible, but the functional and phenotypic characteristics of such cells are not defined. Among cytokines produced by T cells, CCR5 ligands, including macrophage inflammatory protein-1 beta (MIP-1β), compete for the CCR5 coreceptor with HIV, promoting CCR5 internalization and decreasing its availability for virus binding. Interferon (IFN)-γ also has some antiviral activity and has been used as a read-out for T cell immunogenicity. We used cultured ELISpot assays to compare the relative contribution of MIP-1β and IFN-γ to HIV-specific responses. The magnitude of responses was 1.36 times higher for MIP-1β compared to IFN-γ. The breadth of the MIP-1β response (45.41%) was significantly higher than IFN-γ (36.88%), with considerable overlap between the peptide pools that stimulated both MIP-1β and IFN-γ production. Subtype A and D cross-reactive responses were observed both at stimulation and test level, but MIP-1β and IFN-γ responses displayed different effect patterns. We conclude that the MIP-1β ELISpot would be a useful complement to the evaluation of the immunogenicity of HIV vaccines and the activity of adjuvants.
通过CD4(+)和CD8(+) T细胞控制HIV复制或许可行，但此类细胞的功能和表型特征尚未明确。在T细胞产生的细胞因子中，包括巨噬细胞炎性蛋白-1β（MIP-1β）在内的CCR5配体与HIV竞争CCR5共受体，促进CCR5内化并降低其与病毒结合的可用性。干扰素（IFN）-γ也具有一定的抗病毒活性，并已被用作T细胞免疫原性的指标。我们使用培养的ELISpot检测法比较MIP-1β和IFN-γ对HIV特异性反应的相对贡献。MIP-1β的反应强度比IFN-γ高1.36倍。MIP-1β反应的广度（45.41%）显著高于IFN-γ（36.88%），刺激MIP-1β和IFN-γ产生的肽库之间有相当大的重叠。在刺激和检测水平均观察到A亚型和D亚型的交叉反应，但MIP-1β和IFN-γ反应呈现不同的效应模式。我们得出结论，MIP-1β ELISpot将是评估HIV疫苗免疫原性和佐剂活性的有用补充。
