8 results on '"Mashayekhi, Mona"'
Search Results
2. CD4+ T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV
- Author
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Wanjalla, Celestine N., primary, Gabriel, Curtis L., additional, Fuseini, Hubaida, additional, Bailin, Samuel S., additional, Mashayekhi, Mona, additional, Simmons, Joshua, additional, Warren, Christopher M., additional, Glass, David R., additional, Oakes, Jared, additional, Gangula, Rama, additional, Wilfong, Erin, additional, Priest, Stephen, additional, Temu, Tecla, additional, Newell, Evan W., additional, Pakala, Suman, additional, Kalams, Spyros A., additional, Gianella, Sara, additional, Smith, David, additional, Harrison, David G., additional, Mallal, Simon A., additional, and Koethe, John R., additional
- Published
- 2023
- Full Text
- View/download PDF
3. CD4+ T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV.
- Author
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Wanjalla, Celestine N., Gabriel, Curtis L., Fuseini, Hubaida, Bailin, Samuel S., Mashayekhi, Mona, Simmons, Joshua, Warren, Christopher M., Glass, David R., Oakes, Jared, Gangula, Rama, Wilfong, Erin, Priest, Stephen, Temu, Tecla, Newell, Evan W., Pakala, Suman, Kalams, Spyros A., Gianella, Sara, Smith, David, Harrison, David G., and Mallal, Simon A.
- Subjects
FATTY liver ,T cells ,HEART metabolism disorders ,CARNITINE palmitoyltransferase ,NON-alcoholic fatty liver disease ,CHEMOKINE receptors - Abstract
Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1
+ , GPR56+ , and CD57+ /- T cells (termed CGC+ ) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on longterm ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC+ CD4+ T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC+CD4+ T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC+ CD4+ T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4+ T cell subsets, suggesting a potentially greater capacity for fatty acid boxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC+ . Together, this study suggests that among PWH, CGC+ CD4+ T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
4. Leptin Promotes Greater Ki67 Expression in CD4+ T Cells From Obese Compared to Lean Persons Living With HIV
- Author
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Fuseini, Hubaida, primary, Smith, Rita, additional, Nochowicz, Cindy H., additional, Simmons, Joshua D., additional, Hannah, LaToya, additional, Wanjalla, Celestine N., additional, Gabriel, Curtis L., additional, Mashayekhi, Mona, additional, Bailin, Samuel S., additional, Castilho, Jessica L., additional, Hasty, Alyssa H., additional, Koethe, John R., additional, and Kalams, Spyros A., additional
- Published
- 2022
- Full Text
- View/download PDF
5. Adipose Tissue in Persons With HIV Is Enriched for CD4+ T Effector Memory and T Effector Memory RA+ Cells, Which Show Higher CD69 Expression and CD57, CX3CR1, GPR56 Co-expression With Increasing Glucose Intolerance
- Author
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Wanjalla, Celestine N., primary, McDonnell, Wyatt J., additional, Barnett, Louise, additional, Simmons, Joshua D., additional, Furch, Briana D., additional, Lima, Morgan C., additional, Woodward, Beverly O., additional, Fan, Run, additional, Fei, Ye, additional, Baker, Paxton G., additional, Ram, Ramesh, additional, Pilkinton, Mark A., additional, Mashayekhi, Mona, additional, Brown, Nancy J., additional, Mallal, Simon A., additional, Kalams, Spyros A., additional, and Koethe, John R., additional
- Published
- 2019
- Full Text
- View/download PDF
6. CD4 + T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV.
- Author
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Wanjalla CN, Gabriel CL, Fuseini H, Bailin SS, Mashayekhi M, Simmons J, Warren CM, Glass DR, Oakes J, Gangula R, Wilfong E, Priest S, Temu T, Newell EW, Pakala S, Kalams SA, Gianella S, Smith D, Harrison DG, Mallal SA, and Koethe JR
- Subjects
- Humans, Calcium, CX3C Chemokine Receptor 1, Cytomegalovirus, Risk Factors, T-Lymphocyte Subsets, Cardiovascular Diseases, CD4-Positive T-Lymphocytes, HIV Infections
- Abstract
Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1
+ , GPR56+ , and CD57+/- T cells (termed CGC+ ) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC+ CD4+ T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC+ CD4+ T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC+ CD4+ T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4+ T cell subsets, suggesting a potentially greater capacity for fatty acid β-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC+ . Together, this study suggests that among PWH, CGC+ CD4+ T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wanjalla, Gabriel, Fuseini, Bailin, Mashayekhi, Simmons, Warren, Glass, Oakes, Gangula, Wilfong, Priest, Temu, Newell, Pakala, Kalams, Gianella, Smith, Harrison, Mallal and Koethe.)- Published
- 2023
- Full Text
- View/download PDF
7. Leptin Promotes Greater Ki67 Expression in CD4 + T Cells From Obese Compared to Lean Persons Living With HIV.
- Author
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Fuseini H, Smith R, Nochowicz CH, Simmons JD, Hannah L, Wanjalla CN, Gabriel CL, Mashayekhi M, Bailin SS, Castilho JL, Hasty AH, Koethe JR, and Kalams SA
- Subjects
- Adult, Biomarkers, Body Mass Index, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes virology, Cytokines metabolism, Female, Flow Cytometry, HIV Infections virology, Humans, Ki-67 Antigen genetics, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Activation, Lymphocyte Count, Male, Middle Aged, Obesity genetics, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, Gene Expression, HIV Infections genetics, Ki-67 Antigen metabolism, Leptin pharmacology, Obesity metabolism
- Abstract
While antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4
+ T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies demonstrate that obesity, or a body mass index (BMI) ≥ 30 kg/m2 , is positively correlated with greater CD4+ T cell recovery in PLWH on ART. Leptin is a known immunomodulator that is produced in proportion to fat mass and is increased in obese individuals, including PLWH. We hypothesized that CD4+ T cells from obese PLWH have increased cell proliferation and cytokine production compared to cells from lean PLWH, potentially modulated by differential effects of leptin signaling. To test this hypothesis, peripheral blood mononuclear cells from obese and lean PLWH with long-term virologic suppression on the same ART regimen were pretreated with recombinant leptin and then stimulated with anti-CD3/CD28 or PMA/ionomycin to measure Ki67 expression, leptin receptor (LepR) surface expression and cytokine production. In the absence of leptin, Ki67 expression and IL-17A production were significantly higher in CD4+ T cells from obese compared to lean PLWH. However, LepR expression was significantly lower on CD4+ T cells from obese compared to lean PLWH. After leptin treatment, Ki67 expression was significantly increased in CD4+ T cells from obese PLWH compared to the lean participants. Leptin also increased IL-17A production in CD4+ T cells from obese healthy controls. In contrast, leptin decreased IL-17A production in CD4+ T cells from both obese and lean PLWH. Combined, these results demonstrate that obesity is associated with greater CD4+ T cell proliferation among PLWH, and that higher circulating leptin levels in obesity may contribute to improved CD4+ T reconstitution in PLWH initiating ART., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fuseini, Smith, Nochowicz, Simmons, Hannah, Wanjalla, Gabriel, Mashayekhi, Bailin, Castilho, Hasty, Koethe and Kalams.)- Published
- 2022
- Full Text
- View/download PDF
8. Adipose Tissue in Persons With HIV Is Enriched for CD4 + T Effector Memory and T Effector Memory RA + Cells, Which Show Higher CD69 Expression and CD57, CX3CR1, GPR56 Co-expression With Increasing Glucose Intolerance.
- Author
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Wanjalla CN, McDonnell WJ, Barnett L, Simmons JD, Furch BD, Lima MC, Woodward BO, Fan R, Fei Y, Baker PG, Ram R, Pilkinton MA, Mashayekhi M, Brown NJ, Mallal SA, Kalams SA, and Koethe JR
- Subjects
- Adult, Antigens, CD immunology, Antigens, Differentiation, T-Lymphocyte immunology, CD57 Antigens immunology, CX3C Chemokine Receptor 1 immunology, Female, Humans, Immunologic Memory immunology, Lectins, C-Type immunology, Male, Middle Aged, Receptors, G-Protein-Coupled immunology, Adipose Tissue immunology, CD4-Positive T-Lymphocytes immunology, Glucose Intolerance immunology, HIV Infections immunology, T-Lymphocyte Subsets immunology
- Abstract
Chronic T cell activation and accelerated immune senescence are hallmarks of HIV infection, which may contribute to the increased risk of cardiometabolic diseases in people living with HIV (PLWH). T lymphocytes play a central role in modulating adipose tissue inflammation and, by extension, adipocyte energy storage and release. Here, we assessed the CD4
+ and CD8+ T cell profiles in the subcutaneous adipose tissue (SAT) and blood of non-diabetic ( n = 9; fasting blood glucose [FBG] < 100 mg/dL), pre-diabetic ( n = 8; FBG = 100-125 mg/dL) and diabetic ( n = 9; FBG ≥ 126 mg/dL) PLWH, in addition to non- and pre-diabetic, HIV-negative controls ( n = 8). SAT was collected by liposuction and T cells were extracted by collagenase digestion. The proportion of naïve (TNai ) CD45RO- CCR7+ , effector memory (TEM ) CD45RO+ CCR7- , central memory (TCM ) CD45RO+ CCR7+ , and effector memory revertant RA+ (TEMRA ) CD45RO- CCR7- CD4+ and CD8+ T cells were measured by flow cytometry. CD4+ and CD8+ TEM and TEMRA were significantly enriched in SAT of PLWH compared to blood. The proportions of SAT CD4+ and CD8+ memory subsets were similar across metabolic status categories in the PLWH, but CD4+ T cell expression of the CD69 early-activation and tissue residence marker, particularly on TEM cells, increased with progressive glucose intolerance. Use of t-distributed Stochastic Neighbor Embedding (t-SNE) identified a separate group of predominantly CD69lo TEM and TEMRA cells co-expressing CD57, CX3 CR1, and GPR56, which were significantly greater in diabetics compared to non-diabetics. Expression of the CX3 CR1 and GPR56 markers indicate these TEM and TEMRA cells may have anti-viral specificity. Compared to HIV-negative controls, SAT from PLWH had an increased CD8:CD4 ratio, but the distribution of CD4+ and CD8+ memory subsets was similar irrespective of HIV status. Finally, whole adipose tissue from PLWH had significantly higher expression of TLR2, TLR8, and multiple chemokines potentially relevant to immune cell homing compared to HIV-negative controls with similar glucose tolerance.- Published
- 2019
- Full Text
- View/download PDF
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