Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients

Tsunemi, Sachi; Iwasaki, Tsuyoshi; Imado, Takehito; Higasa, Satoshi; Kakishita, Eizo; Shirasaka, Takuma; Sano, Hajime

doi:10.1097/01.aids.0000171401.23243.56

Cited by 125 publications

(119 citation statements)

References 24 publications

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“…SHIV 89.6p -infected animals showed a similar increase in CD152-but not in CD25 hi -expressing CD4 + T cells in the acute phase of infection. As reported for HIV-infected humans (Leng et al, 2002;Tsunemi et al, 2005), CD152 peak expression level correlated inversely with CD4 + count and, in addition, correlated positively with virus load. However, no direct evidence for an immunosuppressive role of these cells is presented here.…”

Section: Zaunderssupporting

confidence: 76%

“…Recently, both events were found to be associated with the development of high virus load in SIVinfected macaques (Sun et al, 2007). Besides a possible direct immunosuppressive effect exerted by several HIV proteins (Cefai et al, 1992;Schindler et al, 2006;Westendorp et al, 1995), the formation of regulatory T cells, specifically the thymus-derived CD25 hi /FOXP3 + /CD152 + subset (Andersson et al, 2005;Estes et al, 2006;Hryniewicz et al, 2006;Kinter et al, 2004;Leng et al, 2002;Nilsson et al, 2006;Tsunemi et al, 2005), was found to be increased in HIV as well as in SIV infection, and was shown to contribute to suppression of HIV-specific immune responses (Kinter et al, 2004;Nilsson et al, 2006;Tsunemi et al, 2005).On the other hand, HIV infection induces a state of chronic immune activation, as shown by increased expression of activation and proliferation markers and increased sensitivity to spontaneous and activationmediated apoptosis induction (Carbone et al, 2000;Gougeon et al, 1993; Hazenberg et al, 2003;Meyaard et al, 1992;Miedema et al, 1988;Ribeiro et al, 2002). Chronic immune activation has been hypothesized Hazenberg et al, 2003; Sousa et al., 2002).…”

mentioning

confidence: 99%

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Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

Koopman

Mortier

Hofman

et al. 2009

Journal of General Virology

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Human immunodeficiency virus (HIV) infection in humans and simian immunodeficiency virus (SIV)infection in macaques are accompanied by a combined early loss of CCR5 (CD195)-expressing CD4 + memory T cells, loss of T-helper function and T-cell hyperactivation, which have all been associated with development of high virus load and disease progression. Here, a cohort of vaccinated simian-human immunodeficiency virus strain 89.6p (SHIV 89.6p )-infected rhesus macaques, where preferential depletion of these memory T-cell subsets does not take place and CD4 + T cells are relatively well maintained, was used to study the role of hyperactivation as an independent factor in the establishment of set-point virus load. In the acute phase of the infection, a transient loss of CD4 + T cells, as well as strong increases in expression of proliferation and activation markers on CD4 + and CD8 + T cells, together with CD152 expression on CD4 + T cells, were observed. Peak expression levels of these markers on CD4 + T cells, but not on CD8 + T cells, were correlated with high virus replication in the chronic phase of the infection. In addition, the peak expression level of these markers was correlated inversely with acute-phase, but not chronic-phase, HIV/SIV-specific gamma interferon responses. These data highlight a central role for an acute but transient CD4 decrease, as well as CD4 + T-cell activation, as independent factors for prediction of set-point levels of virus replication. INTRODUCTIONHuman immunodeficiency virus (HIV) infection in humans and simian immunodeficiency virus (SIV) infection in rhesus macaques are typically characterized by a slow, progressive loss of CD4 + T cells leading to immune incompetence and the onset of opportunistic infections (Fauci, 1988;Lifson et al., 1988). However, already by the early stages of infection, gut-homing CCR5-expressing CD4 memory subsets are being depleted (Brenchley et al., 2004;Li et al., 2005;Mattapallil et al., 2005Mattapallil et al., , 2004Veazey et al., 1998Veazey et al., , 2000 and CD4 + T-helper cell function is impaired (Clerici & Shearer, 1993; Koopman et al., 2001;Lane et al., 1985;McKay et al., 2003;Meyaard et al., 1996;Miedema et al., 1988;Shearer & Clerici, 1991). Recently, both events were found to be associated with the development of high virus load in SIVinfected macaques (Sun et al., 2007). Besides a possible direct immunosuppressive effect exerted by several HIV proteins (Cefai et al., 1992;Schindler et al., 2006;Westendorp et al., 1995), the formation of regulatory T cells, specifically the thymus-derived CD25 hi /FOXP3 + /CD152 + subset (Andersson et al., 2005;Estes et al., 2006;Hryniewicz et al., 2006;Kinter et al., 2004;Leng et al., 2002;Nilsson et al., 2006;Tsunemi et al., 2005), was found to be increased in HIV as well as in SIV infection, and was shown to contribute to suppression of HIV-specific immune responses (Kinter et al., 2004;Nilsson et al., 2006;Tsunemi et al., 2005).On the other hand, HIV infection induces a state of chronic immune activatio...

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Section: Zaunderssupporting

confidence: 76%

mentioning

confidence: 99%

Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

Koopman

Mortier

Hofman

et al. 2009

Journal of General Virology

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“…2b). The relative resistance of this T cell subset to various conditioning regimes (29,47), as well as depletion by HIV infection (48,49), has been reported previously.…”

Section: Characteristics Of T Cell Depletion Induced By Treatment Witsupporting

confidence: 61%

CD25+CD4+ Regulatory T Cells and Memory T Cells Prevent Lymphopenia-Induced Proliferation of Naive T Cells in Transient States of Lymphopenia

Bourgeois¹,

Stockinger²

2006

The Journal of Immunology

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Lymphopenia has been associated with autoimmune pathology and it has been suggested that lymphopenia-induced proliferation of naive T cells may be responsible for the development of immune pathology. In this study we demonstrate that lymphopenia-induced proliferation is restricted to conditions of extreme lymphopenia, because neither naive nor memory T cells transferred into T cell-depleted hosts proliferate unless the depletion exceeds 90% of the peripheral repertoire. Memory CD4 T cells as well as regulatory CD4 T cells proved to be relatively resistant to depletion regimes, and both subsets restrict the expansion and phenotypic conversion of naive T cells by an IL-7R-dependent mechanism. It therefore seems unlikely that lymphopenia-induced proliferation of peripheral T cells causes deleterious side effects that result in immune pathology in states of partial and transient lymphopenia.

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“…The CD4 ϩ CD25 high subset has been counted to represent the CD4 ϩ CD25 ϩ Treg frequency in HBV and HIV-infected patients (35,43). We thus determined the frequency of CD4 ϩ CD25 ϩ Treg by measuring CD4 ϩ CD25 high subset (Fig.…”

Section: Increased Circulating Cd4 ϩ Cd25 ϩ Treg Frequencies In Chronmentioning

confidence: 99%

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

Jin

et al. 2006

The Journal of Immunology

407

363

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CD4+CD25+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self and foreign Ags, but their role in persistent viral infection has not been well-defined. In this study, we investigated whether and where CD4+CD25+ Treg contribute to the development of chronic hepatitis B (CHB). One hundred twenty-one patients were enrolled, including 16 patients with acute hepatitis B, 76 with CHB, and 29 with chronic severe hepatitis B. We demonstrated that in chronic severe hepatitis B patients, the frequencies of CD4+CD25+ Treg in both PBMC and liver-infiltrating lymphocytes were significantly increased and there was a dramatic increase of FoxP3+-cell and inflammatory cell infiltration in the liver compared with healthy controls. In CHB patients, circulating CD4+CD25+ Treg frequency significantly correlates with serum viral load. In acute hepatitis B patients, circulating CD4+CD25+ Treg frequency was initially low and with time, the profile reversed to exhibit an increased number of circulating Treg in the convalescent phase and restored to normal levels upon resolution. In PBMC taken from infected patients, depletion of CD4+CD25+ Treg led to an increase of IFN-γ production by HBV-Ag-stimulated PBMC. In addition, CD4+CD25+ Treg were capable of suppressing proliferation of autologous PBMC mediated by HBV Ags, which probably reflects the generation of HBV-Ag-specific Treg in circulation and in the liver of HBV-infected patients. Together, our findings suggest that CD4+CD25+ Treg play an active role not only in modulating effectors of immune response to HBV infection, but also in influencing the disease prognosis in patients with hepatitis B.

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Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients

Abstract: Increased T Reg frequencies in peripheral blood were related to low peripheral blood CD4 T-cell counts and polarization toward Th2 immune responses in HIV-infected patients.

Cited by 125 publications

References 24 publications

Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

CD25+CD4+ Regulatory T Cells and Memory T Cells Prevent Lymphopenia-Induced Proliferation of Naive T Cells in Transient States of Lymphopenia

Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B

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