Development of virus-specific CD4+ T cells during primary cytomegalovirus infection

Rentenaar, Rob J.; Gamadia, Laila E.; derHoek, Nicolette van; Diepen, F. N. J. Van; Boom, R.; Weel, Jan; Dillen, Pauline M. E. Wertheim-van; Lier, René A. W. van; Berge, Ineke J. M. ten

doi:10.1172/jci8229

Cited by 152 publications

(141 citation statements)

References 29 publications

(23 reference statements)

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…3C). These observations suggest that HCMVspecific CD4 + T cells, previously shown to display an effector-memory phenotype [44,45], may switch the use of costimulatory receptors, becoming CD28 -NKG2D + .…”

Section: Distribution Of Ilt2 Kir and Cd94/nkg2 Nkr On Hcmv-stimulatmentioning

confidence: 73%

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

et al. 2006

View full text Add to dashboard Cite

The human NKG2D killer lectin‐like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3‐kinase (PI3 K) and specifically interacts with different stress‐inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus‐infected cells. This KLR is commonly expressed by human NK cells as well as TCRγδ+ and TCRαβ+CD8+ T lymphocytes, but it has been also detected in CD4+ T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)‐specific CD4+ T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4+NKG2D+ T lymphocytes that coexpressed perforin. NKG2D was detected in CD28– and CD28dull subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR‐dependent activation of CD4+ T cells, triggering proliferation and cytokine production (i.e. IFN‐γ and TNF‐α). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV‐specific CD4+ T lymphocytes and thus may have a role in the response against infected HLA class II+ cells displaying NKG2D ligands.

show abstract

Section: Distribution Of Ilt2 Kir and Cd94/nkg2 Nkr On Hcmv-stimulatmentioning

confidence: 73%

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Accordingly, IL-2 and IL-15 induced expansion of CD27 Ϫ virus-specific T cells, whereas IL-21 promoted outgrowth of CD27 ϩ cells. Although both IL-2 and IL-21 are helper cell-derived cytokines, the differentiation of CMV-specific memory CD8 ϩ T cells to a CD27 Ϫ phenotype upon activation with whole CMV-Ag in combination with peptide shows that the role of IL-21 production by CMV-specific CD4 ϩ memory T cells, reported to have a Th1 profile (42), is limited in accordance with previous reports in which IL-21 was shown to be a Th2 cytokine (43). Whereas production of helper cell-derived cytokines as IL-21 and IL-2 is limited to the antigenic activation phase, IL-15 can be produced by a number of lymphoid and nonlymphoid cells (44).…”

Section: Discussionmentioning

confidence: 99%

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Gamadia

Leeuwen

Remmerswaal³

et al. 2004

The Journal of Immunology

Self Cite

108

View full text Add to dashboard Cite

Based on the expression of the TNFR SFP CD27, two Ag-primed CD8+ T cell subsets can be discerned in the circulation of healthy individuals: CD27+ T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27− T cells, which secrete only IFN-γ and TNF-α. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27+ to a CD27− phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27− CD8+ T cells was found to be linearly related to the total number of CMV-specific CD8+ T cells. In vitro studies revealed that the acquisition of the CD27− phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4+ T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.

show abstract

“…Ki67 up-regulation is observed in acute SIV infection, where within approximately 10 days of SIV inoculation, CD4+Ki67+ T cells are up-regulated and home to lymphoid tissues [36]. Ki67 up-regulation is also observed during acute cytomegalovirus and Epstein Barr virus infections and these Ki67+ T cell subsets are antigen-specific [37,38].…”

Section: Discussionmentioning

confidence: 99%

Immunophenotypic alterations in acute and early HIV infection

Al‐Harthi¹,

MaWhinney²,

Connick³

et al. 2007

Clinical Immunology

View full text Add to dashboard Cite

To understand the extent of immune dysregulation in primary HIV infection (PHI) and the impact of antiretroviral therapy (ART) on restoring these abnormalities, we longitudinally evaluated 52 subjects {Acute Treated (AT); Early Treated (ET); Early Untreated (EU)) for markers of activation, proliferation, and function on T cells. ET and AT patients differed by 0.54 log viral load (VL) at baseline but did not differ thereafter by more than 0.34 log10 VL. AT subjects had higher CD8+ T cell counts and expression of markers indicative of CD8+ T cell activation (CD38), and proliferation (Ki67), at baseline, than ET subjects but were not different post-48 weeks of ART. Although acute PHI is marked by higher level of immune activation than early PHI, virologic and immunologic responses were similar post-ART, suggesting that the extent of immunologic recovery is not negatively impacted by a delay of treatment beyond the acute stage of disease.

show abstract

Development of virus-specific CD4+ T cells during primary cytomegalovirus infection

Cited by 152 publications

References 29 publications

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Immunophenotypic alterations in acute and early HIV infection

Contact Info

Product

Resources

About

Development of virus-specific CD4+ T cells during primary cytomegalovirus infection

Cited by 152 publications

References 29 publications

Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus

Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Immunophenotypic alterations in acute and early HIV infection

Contact Info

Product

Resources

About

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus

Expression and function of NKG2D in CD4⁺ T cells specific for human cytomegalovirus