A fingerprint left by cytomegalovirus infection in the human T cell compartment

Berg, Pablo J. E. J. van de; Stijn, Amber van; Berge, Ineke J. M. ten; Lier, R. A. W. Van

doi:10.1016/j.jcv.2007.10.016

Cited by 72 publications

(55 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 CMVspecific T cells accumulate slowly over time because of repetitive antigenic stimulation (36)(37)(38). Our results indicate that the differentiation of CMV-specific CD4 + T cells occurs early during the course of primary infection.…”

Section: Discussionmentioning

confidence: 65%

Functional Exhaustion of CD4+ T Lymphocytes during Primary Cytomegalovirus Infection

Antoine

Olislagers

Huygens

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Human CMV establishes lifelong persistence after primary infection. Chronic CMV infection is associated with intermittent viral reactivation inducing high frequencies of CD4+ T lymphocytes with potent antiviral and helper properties. Primary CMV infection is characterized by an intense viral replication lasting for several months. The impact of this prolonged exposure to high Ag loads on the functionality of CD4+ T cells remains incompletely understood. In pregnant women with primary CMV infection, we observed that CMV-specific CD4+ T lymphocytes had a decreased capacity to proliferate and to produce IL-2. A very large proportion of CMV-specific CD4+ T cells had downregulated the expression of CD28, a costimulatory molecule centrally involved in the production of IL-2. Unexpectedly, both CD28− and CD28+CD4+ T cells produced low levels of IL-2. This defective production of IL-2 was part of a larger downregulation of cytokine production. Indeed, CMV-specific CD4+ T cells produced lower amounts of IFN-γ and TNF-α and showed lower functional avidity during primary as compared with chronic infection. Increased programmed death-1 expression was observed in CD28+ CMV-specific CD4+ T cells, and programmed death-1 inhibition increased proliferative responses. These results indicate that primary CMV infection is associated with the exhaustion of CMV-specific CD4+ T cells displaying low functional avidity for viral Ags.

show abstract

Section: Discussionmentioning

confidence: 65%

Functional Exhaustion of CD4+ T Lymphocytes during Primary Cytomegalovirus Infection

Antoine

Olislagers

Huygens

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The constitutive expression of IFN-γ message, which resembles stable GZMB expression in murine NK cells (77), may endow CD8 + effector-type T cells with a near-instantaneous capacity to secrete this cytokine upon TCR ligation, a mechanism that may be crucial in rapidly antagonizing virus replication upon reactivation of latent virus. On the downside, the high expression of IFN-γ may subtly increase the overall proinflammatory status in HCMV infection which may be causally related to pathogenic effects of HCMV on the vasculature (15). It is conceivable that the stable expression of IFN-γ in HCMVreactive CD8 + T cells is controlled by a combination of transcription factors, such as T-bet, that are induced during the primary response and maintained throughout the latent state.…”

Section: Discussionmentioning

confidence: 99%

“…HCMV has infected the majority of the global population. In immunocompetent people, primary infection often remains unnoticed, but latent HCMV infection has been associated with vascular pathology and premature immunosenescence (15). These conditions seem to be related to the strong and chronic antiviral response rather than to direct cytopathic effects of the virus (15).…”

Section: Introductionmentioning

confidence: 99%

“…In immunocompetent people, primary infection often remains unnoticed, but latent HCMV infection has been associated with vascular pathology and premature immunosenescence (15). These conditions seem to be related to the strong and chronic antiviral response rather than to direct cytopathic effects of the virus (15). We have previously documented virus-specific CD8 + T cell responses in HCMV-negative transplant recipients experiencing primary HCMV infection after receiving a HCMV-positive kidney (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation

Hertoghs

Moerland

Stijn³

et al. 2010

J. Clin. Invest.

Self Cite

169

202

View full text Add to dashboard Cite

“…Indeed, late-differentiated memory T cells are induced very rapidly after primary CMV infection, even in infants, and persist over long periods (15)(16)(17)(18). Chronological age may add to this effect by simply prolonging the time that the immune system is exposed to the virus.…”

Section: Discussionmentioning

confidence: 99%