Cytomegalovirus infection reduced CD70 expression, signaling and expansion of viral specific memory CD8+ T cells in healthy human adults

作者：Jian Lü, Guobing Chen, Arina Sorokina, Thomas Nguyen, Tonya Wallace, Cuong Nguyen, Christopher Dunn, Stephanie Wang, Samantha Ellis, Guixin Shi, Julia McKelvey, Alexei A. Sharov, Yu‐Tsueng Liu, Jonathan P. Schneck, Nan‐ping Weng · 发表于：Immunity & Ageing · 年份：2022 · DOI：10.1186/s12979-022-00307-7 · 被引用次数：6 · 研究领域：Cytomegalovirus and herpesvirus research、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Abstract Background Cytomegalovirus (CMV) infection leads to effector memory CD8 + T cell expansion and is associated with immune dysfunction in older adults. However, the molecular alterations of CMV-specific CD8 + T cells in CMV infected healthy young and middle-aged adults has not been fully characterized. Results We compared CD8 + T cells specific for a CMV epitope (pp65 495-503 , NLV) and an influenza A virus (IAV) epitope (M1 58-66 , GIL) from the same young and middle-aged healthy adults with serum positive for anti-CMV IgG. Compared to the IAV-specific CD8 + T cells, CMV-specific CD8 + T cells contained more differentiated effector memory (T EM and T EMRA ) cells. Isolated CMV-specific central memory (T CM ) but not naïve (T N ) cells had a significant reduced activation-induced expansion in vitro compared to their IAV-specific counterparts. Furthermore, we found that CD70 expression was reduced in CMV-specific CD28 + CD8 + T CM and that CD70 + T CM had better expansion in vitro than did CD70 - T CM . Mechanistically, we showed that CD70 directly enhanced MAPK phosphorylation and CMV-specific CD8 + T CM cells had a reduced MAPK signaling upon activation. Lastly, we showed that age did not exacerbate reduced CD70 expression in CMV- specific CD8 + T CM cells. Conclusion Our findings showed that CMV infection causes mild expansion of CMV-NLV-specific CD8 + T cells, reduced CD70 expression and signaling, and proliferation of CMV-NLV-specific CD8 + T CM cells in young and ...