Interplay between human cytomegalovirus and dendritic cells in T cell activation

Abstract

Control of human cytomegalovirus (HCMV) infection and prevention of associated diseases in immunocompetent hosts are ensured mainly by CD8+ T cells, in spite of numerous viral tricks to impair antigen presentation and activation of T cells. At sites of primary infection, dendritic cells (DCs) are in the forefront to ensure capture of viral antigens and their capacity to bypass the eVects of viral immunoevasins is crucial in moulding CD8+ T cell repertoire. In HCMV-seropositive donors, the spectrum of CD8+ T cells speciWcities was shown to include immediate-early (IE), early (E) and late (L) gene products, a surprising Wnding if we consider that expression of immunoevasins could paralyse infected DCs from the IE phase of infection. In the present report, we suggest that uninfected dendritic cells could acquire HCMV-antigens derived from input virus or neosynthesis, either in soluble forms or in association with infected dead cells resulting from death-ligand-mediated apoptosis and necrosis. Activation of naïve CD8+ T cells could then occur in lymph nodes through cross-presentation by antigen-loaded DCs, providing an explanation for shape and size of the memory compartment.

Epidemiology of Human Cytomegalovirus (HCMV) in an urban region of Germany: what has changed?

“…Human cytomegalovirus (HCMV) is one of the eight human herpesviruses (herpesvirus hominis-5) and shares their ability to establish persistent infection by using a variety of immune evasion mechanisms [1][2][3][4][5][6]. HCMV-infection has been discovered more than 100 years ago by histological analysis of organs investigated in people who had died from other causes.…”

Paracrine inhibition of GM-CSF signaling by human cytomegalovirus in monocytes differentiating to dendritic cells

“…However, this is always incomplete because the virus immune evasion functions are circumvented by the host. 3 Because monocytes are the precursors of DCs in vivo and HCMV may infect them to further establish latency, we examined the effects of infection on monocyte differentiation and DC dysfunction.…”

“…We have developed a working hypothesis that these virus-induced changes can be overcome by uninfected DC cross-presenting Ags to CD8 ϩ T cells. 3 Monocytes are primary targets of HCMV, can harbor latent virus, and are a source of inflammatory DCs in vivo. [4][5][6] We therefore assumed that DC dysfunction was because of abnormalities arising during the differentiation of their monocyte precursors.…”

Measurement of cytotoxic T lymphocyte activity of human cytomegalovirus seropositive individuals by a highly sensitive coupled luminescent method

“…We have used CTLs from HCMV seropositive individuals for this study since HCMV, an important pathogen in immunocompromised individuals, is currently being investigated for a plethora of diVerent questions and aspects [36][37][38][39]. The use of CLM in adaptive immune cells like CTLs is therefore of great signiWcance since it provides a safe and fast procedure for the measurement of antigenspeciWc CTLs function, which is crucial for the analysis of the pathogenesis of infectious diseases and to evaluate the eYcacy of immunotherapies in HLA-restricted setting.…”

“…These peptides require no further proteolytic processing to be active, and they are capable of sensitizing the transporter associated with antigen presentation (TAP)-deWcient cell line, T2, for lysis by appropriate HLA-restricted CTLs [25]. HCMV-pp65 HLA-A2-restricted peptide has commonly been used in experiments to monitor CTLs activation [26][27][28][29][30][31].…”