Immunophenotype and Function of CD38-Expressing CD4+ and CD8+ T Cells in HIV-Infected Patients Undergoing Suppressive Combination Antiretroviral Therapy

Cannizzo, Elvira S.; Bellistrì, Giusi M.; Casabianca, Anna; Tincati, Camilla; Iannotti, Nathalie; Barco, Ambra; Orlandi, Chiara; Monforte, Antonella d’Arminio; Marchetti, Giulia

doi:10.1093/infdis/jiu634

Cited by 14 publications

(12 citation statements)

References 10 publications

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“…Therefore, we decided to utilize the marker CD38 in order to investigate the expression of CD300a receptor on activated CD4+ T cells from HIV-1 infected people. In agreement with previous publications ( 30 , 33 ), we observed that, except for the naïve subset, all CD4+ T cells from cART naïve HIV-1 infected patients express higher percentages of CD38+ cells than the cells from healthy donors or cART-treated patients (Figure S4A in Supplementary Material). There were no significant differences in the frequency of CD38+ cells on naïve CD4+ T cells from healthy subjects and infected patients (Figure S4A in Supplementary Material).…”

Section: Resultssupporting

confidence: 93%

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

et al. 2018

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The ability of the CD300a inhibitory receptor to modulate immune cell functions and its involvement in the pathogenesis of many diseases has aroused a great interest in this molecule. Within human CD4+ T lymphocytes from healthy donors, the inhibitory receptor CD300a is differentially expressed among different T helper subsets. However, there are no data about the expression and regulation of CD300a receptor on CD4+ T cells from human immunodeficiency virus (HIV)-1-infected patients. The objective of this study was to investigate the expression of CD300a on CD4+ T cells from HIV-infected patients on suppressive combined antiretroviral therapy (cART) and cART naïve patients. Our results have demonstrated that the expression levels of this inhibitory receptor were higher on CD4+ T cells from HIV-1 infected subjects compared with healthy donors, and that cART did not reverse the altered expression of CD300a receptor in these patients. We have observed an increase of CD300a expression on both PD1+CD4+ and CD38+CD4+ T cells from HIV-1 infected people. Interestingly, a triple positive (CD300a+PD1+CD38+) subset was expanded in naïve HIV-1 infected patients, while it was very rare in healthy donors and patients on cART. Finally, we found a negative correlation of CD300a expression on CD4+ T lymphocytes and some markers associated with HIV-1 disease progression. Thus, our results show that HIV-1 infection has an impact in the regulation of CD300a inhibitory receptor expression levels, and further studies will shed light into the role of this cell surface receptor in the pathogenesis of HIV infection.

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Section: Resultssupporting

confidence: 93%

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

et al. 2018

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“…Here, we first analysed PD1 and CD38 expression on different CD8+ T cell subsets from HIV-1+ individuals, confirming that our results were in accordance with previous publications ( Supplementary Fig. 2a,b) 45,46 . Next, we determined the MFI of CD300a on memory, effector memory and TEM CD8+ T cells expressing PD1 and CD38 in untreated HIV-1+ subjects ( Fig.…”

Section: Association Of Cd300a Expression With Markers Of Hiv-1 Infecsupporting

confidence: 92%

“…2a) 45 , and on the other hand, because they constitutively express CD38 in resting conditions ( Supplementary Fig. 2b) 41,46 . Therefore, CD38 is an unsuitable activation marker for naïve CD8+ T cells.…”

Section: Association Of Cd300a Expression With Markers Of Hiv-1 Infecmentioning

confidence: 99%

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Vitallé

Terrén

Gamboa-Urquijo

et al. 2020

Sci Rep

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CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a GagHIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response. CD8+ T cells are very important effectors in the control and clearance of viruses through several mechanisms, including granule exocytosis and cytokine production 1-3 . Many reports have shown that CD8+ T cells play a very important role in the control of viral replication during the acute phase of human immunodeficiency virus (HIV)−1 infection, contributing to the initial control of infection 1,3-7 . Thus, a large number of current studies are focused on the search of new therapies with the aim of inducing a potent and effective HIV specific CD8+ T cell response [8][9][10] .After antigen recognition and subsequent activation, CD8+ T cells up-regulate the expression of inhibitory receptors with the aim of preventing an excessive response that, if not properly regulated, could be harmful to the host 11,12 . During chronic stimulation, as for example persistent exposure to HIV antigens, CD8+ T cells became progressively dysfunctional and exhausted, and the expression of inhibitory receptors persists 13 . Exhaustion is a process characterized by a loss of proliferative capacity, differentiation and effector functions 12,14,15 . There are several inhibitory receptors that are expressed on exhausted T cells. For instance, programed cell death-1 (PD1) is known to be involved in the regulation of CD8+ T lymphocytes function during chronic HIV-1 infection and their expression correlates with disease progression 11,12,15 . In addition to the negative regulatory role of these inhibitory receptors, they also mark antigen specific T cells. For example, it has been described that PD1 on CD8+ T cells identifies the repertoire of clonally expanded tumor-reactive lymphocytes and situations of chronic inflammation, which is ...

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“…Both receptors are important for inflammatory responses and cell migration. CD38 is characteristically raised in chronic inflammation and is associated with an enhanced ability to produce IFN-γ ( 63 , 64 ). CCR6 is expressed on effector memory populations that contribute to recall responses ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Progesterone Modulation of Pregnancy-Related Immune Responses

2018

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Progesterone (P4) is an important steroid hormone for the establishment and maintenance of pregnancy and its functional withdrawal in reproductive tissue is linked with the onset of parturition. However, the effects of P4 on adaptive immune responses are poorly understood. In this study, we took a novel approach by comparing the effects of P4 supplementation longitudinally, with treatment using a P4 antagonist mifepristone (RU486) in mid-trimester pregnancies. Thus, we were able to demonstrate the immune-modulatory functions of P4. We show that, in pregnancy, the immune system is increasingly activated (CD38, CCR6) with greater antigen-specific cytotoxic T cell responses (granzyme B). Simultaneously, pregnancy promotes a tolerant immune environment (IL-10 and regulatory-T cells) that gradually reverses prior to the onset of labor. P4 suppresses and RU486 enhances antigen-specific CD4 and CD8 T cell inflammatory cytokine (IFN-γ) and cytotoxic molecule release (granzyme B). P4 and RU486 effectively modulate immune cell-mediated interactions, by regulating differentiated memory T cell subset sensitivity to antigen stimulation. Our results indicate that P4 and RU486, as immune modulators, share a reciprocal relationship. These data unveil key contributions of P4 to the modulation of the maternal immune system and suggests targets for future modulation of maternal immune function during pregnancy.

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Immunophenotype and Function of CD38-Expressing CD4+ and CD8+ T Cells in HIV-Infected Patients Undergoing Suppressive Combination Antiretroviral Therapy

Cited by 14 publications

References 10 publications

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

Altered Expression of CD300a Inhibitory Receptor on CD4+ T Cells From Human Immunodeficiency Virus-1-Infected Patients: Association With Disease Progression Markers

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Progesterone Modulation of Pregnancy-Related Immune Responses

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