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

Jian Lu, Guobing Chen, Arina Sorokina, Thomas Nguyen, Tonya Wallace, Cuong Nguyen, Christopher Dunn, Stephanie Wang, Samantha Ellis, Guixin Shi, Julia McKelvey, Alexei Sharov, Yu Tsueng Liu, Jonathan Schneck, Nan ping Weng

Research output: Contribution to journalArticlepeer-review


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 (pp65495-503, NLV) and an influenza A virus (IAV) epitope (M158-66, 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 (TEM and TEMRA) cells. Isolated CMV-specific central memory (TCM) but not naïve (TN) 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+ TCM and that CD70+ TCM had better expansion in vitro than did CD70- TCM. Mechanistically, we showed that CD70 directly enhanced MAPK phosphorylation and CMV-specific CD8+ TCM cells had a reduced MAPK signaling upon activation. Lastly, we showed that age did not exacerbate reduced CD70 expression in CMV- specific CD8+ TCM 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+ TCM cells in young and middle-aged healthy adults and revealed an age-independent and CMV infection-specific impact on CD8+ memory T cells.

Original languageEnglish (US)
Article number54
JournalImmunity and Ageing
Issue number1
StatePublished - Dec 2022


  • Activation
  • CD70
  • CMV-specific CD8 T cells
  • Chronic infection
  • Expansion

ASJC Scopus subject areas

  • Aging
  • Immunology


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