In vivo expansion of CD4+CD45RO-CD25+ T cells expressing foxP3 in IL-2-treated HIV-infected patients

Sereti, Irini; Imamichi, Hiromi; Natarajan, Ven; Imamichi, Tomozumi; Ramchandani, Meena; Badralmaa, Yunden; Berg, Steve C.; Metcalf, Julia A.; Hahn, Barbara; Shen, Jean; Powers, April; Davey, Richard T.; Kovacs, Joseph A.; Shevach, Ethan M.; Lane, H. Clifford

doi:10.1172/jci24307

Cited by 110 publications

(94 citation statements)

References 48 publications

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“…First, the lack of a specific marker for Treg has led to the assumption that only CD4ϩ,CD25 high T cells represent human Treg. (25,(38)(39)(40). However, it is unclear whether the reported reduction in the number of CD4ϩ,CD25 high Treg in SLE is compensated by an increase in the number of CD25 low ,Foxp3ϩ Treg that was not analyzed in previous studies.…”

Section: Discussionmentioning

confidence: 97%

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

Franz¹,

Fritzsching²,

Riehl³

et al. 2007

Arthritis & Rheumatism

122

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Objective. To define the phenotype and function of CD4؉,CD25؉ regulatory T cells (Treg) in patients with cutaneous lupus erythematosus (CLE), a heterogeneous autoimmune disease characterized primarily by inflammatory skin lesions.Methods. The number of Treg in skin specimens obtained from patients with various subtypes of CLE was investigated by immunohistochemical analysis, using anti-Foxp3 and anti-CD4 monoclonal antibodies. Furthermore, characterization of peripheral blood CD4؉,CD25؉ Treg from normal healthy donors and patients with CLE was carried out by flow cytometry, analyzing the expression of Foxp3 and Treg subpopulations. We also purified CD4؉,CD25 high Treg obtained from patients with CLE and tested the sensitivity of these cells to CD95L-mediated apoptosis.Results. Quantitative analysis of CD4؉ T cells in skin lesions from patients with CLE revealed that the number was similar to that in lesions from patients with other chronic inflammatory diseases, but the number of Foxp3؉ Treg in CLE was significantly reduced. There was no correlation between disease subtype and the frequency of Foxp3؉ Treg in the skin of patients with CLE. In peripheral blood, no significant differences were observed in the number and phenotype of CD4؉,CD25؉ Treg or in the sensitivity to apoptosis of CD4؉,CD25 high Treg derived from patients with CLE and those derived from normal healthy donors.Conclusion. These data suggest that an organspecific abnormality of Treg in the skin underscores the importance of analyzing Treg in the affected tissue. Such a local process might give insight into the pathogenic mechanisms of CLE and differs from a global peripheral dysfunction as reported for patients with a systemic manifestation of the disease.

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Section: Discussionmentioning

confidence: 97%

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

Franz¹,

Fritzsching²,

Riehl³

et al. 2007

Arthritis & Rheumatism

122

View full text Add to dashboard Cite

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“…139 The somewhat paradoxical effect of IL-2 may be explained by the increase of distinct CD4CCD25C expressing high level of FOXP3, defined as cytokine-induced na€ ıve (CEN) T-cells, which could act as T regulatory cells with suppressor activity. [140][141][142][143] IL-7 is another key cytokine which role is impaired in HIV infection, mostly thank to impairment of receptor signaling via CD127 (a component of IL-7 receptor [IL-7R]). [144][145] IL-7 is crucial for T cell development and homeostasis thanks to its anti-apoptotic and co-stimulatory proliferative signals 146 and in untreated patients with HIV infection high levels of IL-7 reflects a compensatory loop mechanism to contrast HIV-induced lymphopenia (Fig.…”

Section: New Treatment Strategies and Immunotherapy In Aging Hiv Patimentioning

confidence: 99%

Immunosenescence and hurdles in the clinical management of older HIV-patients

2017

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People living with HIV (PLWH) who are treated with effective highly active antiretroviral therapy (HAART) have a similar life expectancy to the general population. Moreover, an increasing proportion of new HIV diagnoses are made in people older than 50 y. The number of older HIVinfected patients is thus constantly growing and it is expected that by 2030 around 70% of PLWH will be more than 50 y old. On the other hand, HIV infection itself is responsible for accelerated immunosenescence, a progressive decline of immune system function in both the adaptive and the innate arm, which impairs the ability of an individual to respond to infections and to give rise to long-term immunity; furthermore, older patients tend to have a worse immunological response to HAART.In this review we focus on the pathogenesis of HIV-induced immunosenescence and on the clinical management of older HIV-infected patients.

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“…In response to IL-2 treatment, CD4 ϩ CD25 ϩ CD45RO Ϫ T cells rapidly expanded. 39 Similarly, CD4 ϩ CD25 ϩ CD45RO Ϫ T cells have been reported to expand during rheumatoid arthritis. 40 Although CD4 ϩ CD25 ϩ CD45RO Ϫ T cells expressed high amounts of FOXP3, Sereti and coworkers considered these cells to be different from T regs because they were CD45RO lo , CD25 int , and also weak suppressors unlike CD4 ϩ CD25 hi T regs .…”

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confidence: 96%

“…Moreover, CD4 ϩ CD25 ϩ CD45RO Ϫ T cells were reported to be CD95 lo and resistant to CD95L-mediated apoptosis. 39 Because these properties are all features of naive T regs , we consider it highly likely that the reported CD4 ϩ CD25 ϩ CD45RO Ϫ T cells in treated HIV patients predominantly contained naive T regs . Because FOXP3 was not analyzed at a single-cell level by flow cytometry, contamination of naive T reg cells with T convs within the analyzed CD4 ϩ CD25 ϩ CD45RO Ϫ T cells could not be detected.…”

mentioning

confidence: 99%

Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death

Fritzsching

Oberle

Pauly

et al. 2006

Blood

148

116

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IntroductionThere is now clear evidence that CD4 ϩ T cells contain a population of naturally immunosuppressive T cells characterized by constitutive expression of CD25, CTLA-4, and FOXP3. 1 Because not all potentially autoreactive T cells are deleted in the thymus, 2,3 peripheral control of T-cell responses by naturally occurring CD4 ϩ CD25 ϩ FOXP3 ϩ immunoregulatory T cells (T regs ) is crucial to prevent autoimmunity. 1 Depletion of T regs contributes to the induction of severe autoimmune diseases in animal models, and several studies have reported a defect of T regs in various human autoimmune diseases. 1,4,5 Despite extensive research to unravel the immunosuppressive function of T reg , the exact molecular mechanism of immunosuppression is still elusive. Promising targets for pharmacologic mimicking of T regs function remain undefined. Consequently, direct use of T regs for therapy is currently under examination. Therapeutic expansion or depletion of T regs with defined antigen specificity offers new treatment options for human diseases. 6 Because accumulation of T regs has been shown to be detrimental in cancer, 7 new insights into mechanisms of T reg homeostastis are required.To gain new insight into the modulation of T reg numbers as well as their antigen specificity, the development of natural T regs during ontogeny and in the adult needs to be explored. The peripheral T reg compartment consists mainly of thymus-derived T regs . 1 However, under specific circumstances T regs can also be generated out of conventional T cells (T convs ) (eg, if the antigen is targeted to immature dendritic cells [DCs]). [8][9][10] It has yet to be established how much "converted" T regs contribute to the total number of T regs in the periphery of adult mice and humans.At a given time, the overall number of T regs is defined by a balance of generation and demise of T regs . At the end of an immune reaction, T cells are depleted by apoptosis. Activation-induced cell death (AICD) through CD95/CD95L has been described as such an apoptosis-inducing mechanism. 11 While naive T cells are CD95 Ϫ and resistant to apoptosis induction, activated T cells (CD45RO hi ) up-regulate CD95 and become sensitive to apoptosis. Upon T-cell receptor (TCR) restimulation, activated effector T cells (T effs ) up-regulate CD95L and induce AICD through crosslinking of CD95 by CD95L. AICD eliminates T effs after an immune response and contributes to T-cell homeostasis. We have previously shown that most T regs constitutively express CD95 and can easily be killed via crosslinking of this death receptor by CD95L. 12 Together with the fact that most T regs express high levels of CD45RO, we contributed expertise in microarray analysis; J.P. contributed clinical samples; P.K. analyzed data and assisted in writing the paper; O.L. contributed clinical samples and assisted in writing the paper; and E.S.-P. designed research and wrote the paper.The online version of this article contains a data supplement. For personal use only. on April 5, 2019. by guest www....

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In vivo expansion of CD4+CD45RO-CD25+ T cells expressing foxP3 in IL-2-treated HIV-infected patients

Cited by 110 publications

References 48 publications

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

Immunosenescence and hurdles in the clinical management of older HIV-patients

Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death

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