The CD4+ T Cell Response to Human Cytomegalovirus in Healthy and Immunocompromised People.
Frontiers in cellular and infection microbiology
Frontiers Media S.A.
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Lim, E. Y., Jackson, S., & Wills, M. (2020). The CD4+ T Cell Response to Human Cytomegalovirus in Healthy and Immunocompromised People.. Frontiers in cellular and infection microbiology, 10 202. https://doi.org/10.3389/fcimb.2020.00202
While CD8+ T cells specific for human cytomegalovirus (HCMV) have been extensively studied in both healthy HCMV seropositive carriers and patients undergoing immunosuppression, studies on the CD4+ T cell response to HCMV had lagged behind. However, over the last few years there has been a significant advance in our understanding of the importance and contribution that CMV-specific CD4+ T cells make, not only to anti-viral immunity but also in the potential maintenance of latently infected cells. During primary infection with HCMV in adults, CD4+ T cells are important for the resolution of symptomatic disease, while persistent shedding of HCMV into urine and saliva is associated with a lack of HCMV specific CD4+ T cell response in young children. In immunosuppressed solid organ transplant recipients, a delayed appearance of HCMV-specific CD4+ T cells is associated with prolonged viremia and more severe clinical disease, while in haematopoietic stem cell transplant recipients, it has been suggested that HCMV-specific CD4+ T cells are required for HCMV-specific CD8+ T cells to exert their anti-viral effects. In addition, adoptive T-cell immunotherapy in transplant patients has shown that the presence of HCMV-specific CD4+ T cells is required for the maintenance of HCMV-specific CD8+ T cells. HCMV is a paradigm for immune evasion. The presence of viral genes that down-regulate MHC class II molecules and the expression of viral IL-10 both limit antigen presentation to CD4+ T cells, underlining the important role that this T cell subset has in antiviral immunity. This review will discuss the antigen specificity, effector function, phenotype and direct anti-viral properties of HCMV specific CD4+ T cells, as well as reviewing our understanding of the importance of this T cell subset in primary infection and long-term carriage in healthy individuals. In addition, their role and importance in congenital HCMV infection and during immunosuppression in both solid organ and haemopoietic stem cell transplantation is considered.
CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Humans, Cytomegalovirus, Cytomegalovirus Infections, Immunocompromised Host, Adult, Child, Child, Preschool
Wellcome Trust (via University College London (UCL)) (Ref 17/0008 539724)
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External DOI: https://doi.org/10.3389/fcimb.2020.00202
This record's URL: https://www.repository.cam.ac.uk/handle/1810/304500
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