Decreased Immune Activation in Resistance to HIV‐1 Infection Is Associated with an Elevated Frequency of CD4+CD25+FOXP3+Regulatory T Cells

Card, Catherine M.; McLaren, Paul J.; Wachihi, Charles; Kimani, Joshua; Plummer, Francis A.; Fowke, Keith R.

doi:10.1086/597801

Cited by 146 publications

(153 citation statements)

References 14 publications

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“…Women included in the HIV 2 FSW group had been enrolled in the sex worker cohort for at least 3 y, and some of them thus met the criterion of being relatively HIV resistant (24). A low immune activation state can be associated with resistance to heterosexual HIV transmission in the present cohort, as previously identified in blood, cervical mononuclear cells, and cervicovaginal secretions (36)(37)(38). Thus, the relatively low CD4 cell counts and immune activation status that we observed at the genital tissue level for some of the HIV 2 FSW women may reflect and represent this rare phenotype of HIV-resistant individuals.…”

Section: Discussionmentioning

confidence: 53%

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Hirbod

Kimani

Tjernlund

et al. 2013

The Journal of Immunology

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Studies using genital tissue samples from HIV-infected women might provide important information about HIV susceptibility and transmission. In this study, ectocervical biopsies were obtained from 20 HIV-seropositive (HIV+) Kenyan female sex workers (FSW) and 20 HIV-seronegative lower risk (HIV− LR) women. To control for the impact of sex work, 20 HIV− FSW were also recruited. Immune molecules were assessed in situ by immunohistochemistry and for mRNA expression by quantitative PCR. The HIV+ women were reportedly infected for a median of 3 y (1–21 y), with a median viral load of 11,735 copies/ml (20–648,000 copies/ml). These women had significantly lower CD4 blood cell counts than the HIV− LR women but comparable levels of CD4 expression in ectocervix. Whereas cellular markers were similar between the HIV+ group and the HIV− LR women, the HIV-binding molecules CCR5, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as the inflammatory markers CD69, IFN-γ, IL-6, and IL-22 were significantly upregulated in the HIV+ group. As compared with the HIV− FSW women, the HIV+ women had significantly upregulated levels of CD4, CD3, CCR5, Langerin, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as inflammatory cytokines. The CD4 cell depletion previously seen in the gut mucosa of HIV-infected individuals was thus not observed in the ectocervical mucosa. Stable CD4 cell expression and local immune activation in the lower female genital tract may promote viral replication and genital shedding and increase the risk of sexual HIV transmission.

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Section: Discussionmentioning

confidence: 53%

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Hirbod

Kimani

Tjernlund

et al. 2013

The Journal of Immunology

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“…Treg frequency has been shown to inversely correlate with immune activation (2,3). Furthermore, deregulation of Treg function and Treg/Th17 cell ratios may impair beneficial mucosal Th17 responses during chronic infection (4).…”

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confidence: 99%

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Manches

Fernandez

Plumas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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HIV modulates plasmacytoid dendritic cell (pDC) activation via Tolllike receptor 7, inducing type I IFN and inflammatory cytokines. Simultaneously, pDCs up-regulate the expression of indoleamine 2,3 dioxygenase (IDO), which is essential for the induction of regulatory T cells (Tregs), which function to down-modulate immune activation. Here we demonstrate the crucial importance of the noncanonical NF-κB pathway in the establishment of this immunoregulatory phenotype in pDCs. In response to HIV, the noncanonical NF-κB pathway directly induces IDO and involves the recruitment of TNF receptorassociated factor-3 to the Toll-like receptor/MyD88 complex, NF-κB-inducing kinase-dependent IκB kinase-α activation, and p52/RelB nuclear translocation. We also show that pDC-induced Tregs can inhibit conventional DC (cDC) maturation partially through cytotoxic T-lymphocyte antigen (CTLA)-4 engagement. Furthermore, CTLA-4 induces IDO in cDCs in a NF-κB-inducing kinase-dependent way. These CTLA-4-conditioned cDCs can in turn induce Treg differentiation in an IDO-dependent manner. Thus, the noncanonical NF-κB pathway is integral in controlling immunoregulatory phenotypes of both pDCs and cDCs.

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“…항바이러스 면역반응을 억제하는 조절 T림프구의 발현양상 은 HIV, HCV 등에 의한 바이러스 감염 환자의 임상경과에 큰 영향을 미치는 것으로 보고되었다 (Rouse et al, 2006;Card et al, 2009) (Chen and Shi, 2006) (Table 1). (Chen, 2004).…”

Section: Foxp3+ Tregsunclassified

The Roles of Immune Regulatory Factors FoxP3, PD-1, and CTLA-4 in Chronic Viral Infection

Cho¹

2013

The Korean Journal of Microbiology

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Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) cause viral infections that lead to chronic diseases. When they invade human body, virus specific T cells play an important role in antiviral effector functions including killing virus-infected cells and helping Golden-Mason et al., 2007). PD-1은 항원제시세포가 발현하는 PD-L1/PD-L2와 결합 하며, CTLA-4는 CD28과 경쟁적으로 B7-1 (또는 B7-2)과 결합 함으로써 두 수용체 모두 T림프구의 활성을 억제하는 기능을 가 진다 (Fife and Bluestone, 2008).급·만성을 포함하는 바이러스 감염에서 초기 T림프구의 표면 항원은 앞서 제시한 CD28 발현이 두드러지며, 임상경과상 흔히 급성기라고 표현되는 중기 T림프구에서는 CD28 뿐만 아니라

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Decreased Immune Activation in Resistance to HIV‐1 Infection Is Associated with an Elevated Frequency of CD4⁺CD25⁺FOXP3⁺Regulatory T Cells

Cited by 146 publications

References 14 publications

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

The Roles of Immune Regulatory Factors FoxP3, PD-1, and CTLA-4 in Chronic Viral Infection

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