Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation

Eggena, Mark; Barugahare, Banson; Jones, Norman; Okello, Martin; Mutalya, Steven; Kityo, Cissy; Mugyenyi, Peter; Cao, Huyen

doi:10.4049/jimmunol.174.7.4407

Cited by 325 publications

(327 citation statements)

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“…In the initial phase, higher Treg activity induces a paradoxical effect of stabilized CD4 + levels by reducing CD8 + T activity (Kinter et al 2004, Eggena et al 2005. Therefore, the progressive reduction in Tregs results in an increased Th2 CD4 + T lymphocyte response to environmental allergens.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, this contradictory effect has been attributed to functional and quantitative alterations in regulatory T cells (Kinter et al 2004, Eggena et al 2005). These observations suggest that immunological alterations secondary to HIV infection alter the normal allergy control mechanisms, thus permitting an increase in the clinical expression of allergic diseases (Bacot et al 1997).…”

mentioning

confidence: 99%

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Laboratorial atopy markers in children with human immunodeficiency virus

Cruz

Carvalho

Santos

et al. 2010

Mem. Inst. Oswaldo Cruz

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Laboratorial atopy markers in children with human immunodeficiency virus

Cruz

Carvalho

Santos

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…However, the circulating frequency of CD4 + Treg cells has not been found to show any correlation with the magnitude of HIV‐specific T‐cell responses,276, 277, 278 leaving the contribution of CD4 + Treg cells to regulation of virus‐specific T‐cell responses in HIV‐infected individuals unclear. Their role in suppressing immune activation is also uncertain.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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“…Thus, several groups have shown that Tregs numbers are either decreased [8,96,97,104,105] or increased [91,95,100,101] in HIV-1 infection. A clearer understanding of Tregs in disease progression has come to light with the use of monkey models of HIV infection.…”

Section: Relative Levels Of Foxp3 and Treg During Hiv-1 Infection Andmentioning

confidence: 99%

“…Epple et al [91] Montes et al [92] Mozos et al [93] Lim et al [94] Andersson et al [95] Epple et al [91] Nilsson et al [100] ↓ Oswald-Richter et al [8] Andersson et al [95] Apoil et al [96] Eggena et al [97]; Baker et al [98] Mozos et al [93] Treg levels a …”

Section: Treg Levels Amentioning

confidence: 99%

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

et al. 2008

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FoxP3 + CD4 + CD25 + regulatory T (Treg) cells are implicated in a number of pathologic processes including elevated levels in cancers and infectious diseases, and reduced levels in autoimmune diseases. Treg cells are activated to modulate immune responses to avoid over-reactive immunity. However, conflicting findings are reported regarding relative levels of Treg cells during HIV-1 infection and disease progression. The role of Treg cells in HIV-1 diseases (aberrant immune activation) is poorly understood due to lack of a robust model. We summarize here the regulation and function of Foxp3 in Treg cells and in modulating HIV-1 replication. Based on recent findings from SIV/monkey and HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1 infection and immuno-pathogenesis is discussed. KeywordsRegulatory T cells; AIDS; Chromatin; Epigenetic; Humanized mouse; DKO-hu; ONTAK Regulatory T cells play an important role in self immune tolerance and in balanced immune responsesThe regulation of immune tolerance is a critical aspect of immunology. The balance between recognition of self versus non-self is essential for maintenance of immune homeostasis. Regulatory T cells (CD4 + CD25 + ) are a crucial component for the control of deleterious effects from excessive immune responses as seen in autoimmune disease or allergic insult [1,2]. Treg cells have been implicated in a number of pathologic processes including elevated levels in cancers [3][4][5] and infectious diseases [6][7][8][9], and reduced levels in autoimmune diseases [1,[10][11][12][13]. It is apparent that Treg cells are induced (or recruited and expanded) by most infections to modulate host immune responses to avoid overreactive immunity (Fig. 1). As a result, Treg play a critical role in immune responses, vaccinations as well as in immunopathogenesis of pathogens. For example, Leishmania infection leads to induction of Treg that help to maintain the balance of immune response and pathogen persistence [18,19]. For the host, persistence of the pathogen is beneficial to maintain effective immunity against these pathogens [18]. In a number of chronic viral infections, Treg are induced to subdue the anti-viral immune responses and allow persistent infection. Mechanisms of CD4 T-cell differentiationT-cell lineage commitment and activation of T cells are usually accompanied by changes in patterns of gene expression. During T-cell responses, T helper (Th) progenitor cells will undergo Th1 or Th2 lineage commitments involving well-defined initiation cytokines, transcription factors, and effector cytokines. Expression of T-bet and GATA3 in Th1 and Th2 cells, respectively, is epigenetically regulated by histone modification and DNA methylation. As T lineage determinants, T-bet or GATA3 are also involved in epigenetically reprogramming the T-cell genome to silence the Th2 or Th1 effector cytokines, respectively, and to activate Th1 or Th2 cytokine genes for transcription (Fig. 2). Similarly, Th17 cell differentiation requires IL-6/TGF-β (mo...

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Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation

Cited by 325 publications

References 61 publications

Laboratorial atopy markers in children with human immunodeficiency virus

Laboratorial atopy markers in children with human immunodeficiency virus

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

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