Faculty Opinions recommendation of Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy.

The interaction of neutrophils with T cells has been the subject of debate and controversies. Previous studies have suggested that neutrophils may suppress or activate T cells. Despite these studies, the interaction between neutrophils and T cells has remained a largely unexplored field. Here, based on our RNA sequencing (RNA-seq) analysis, we found that neutrophils have differential transcriptional and functional profiling depending on the CD4 T-cell count of the HIV-infected individual. In particular, we identified that neutrophils in healthy individuals express surface Galectin-9 (Gal-9), which is down-regulated upon activation, and is consistently down-regulated in HIV-infected individuals. However, down-regulation of Gal-9 was associated with CD4 T-cell count of patients. Unstimulated neutrophils express high levels of surface Gal-9 that is bound to CD44, and, upon stimulation, neutrophils depalmitoylate CD44 and induce its movement out of the lipid raft. This process causes the release of Gal-9 from the surface of neutrophils. In addition, we found that neutrophil-derived exogenous Gal-9 binds to cell surface CD44 on T cells, which promotes LCK activation and subsequently enhances T-cell activation. Furthermore, this process was regulated by glycolysis and can be inhibited by interleukin (IL)-10. Together, our data reveal a novel mechanism of Gal-9 shedding from the surface of neutrophils. This could explain elevated plasma Gal-9 levels in HIV-infected individuals as an underlying mechanism of the well-characterized chronic immune activation in HIV infection. This study provides a novel role for the Gal-9 shedding from neutrophils. We anticipate that our results will spark renewed investigation into the role of neutrophils in T-cell activation in other acute and chronic conditions, as well as improved strategies for modulating Gal-9 shedding.

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A Subset of Extreme Human Immunodeficiency Virus (HIV) Controllers Is Characterized by a Small HIV Blood Reservoir and a Weak T-Cell Activation Level

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx064 ◽

2017 ◽

Vol 4 (2) ◽

Cited By ~ 22

Author(s):

Etienne Canouï ◽

Camille Lécuroux ◽

Véronique Avettand-Fenoël ◽

Marine Gousset ◽

Christine Rouzioux ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

T Cell ◽

Cell Count ◽

T Cell Activation ◽

Cell Activation ◽

Cd4 T Cell ◽

Hiv Dna ◽

Immunodeficiency Virus ◽

Cd4 T Cell Count

Abstract Background Human immunodeficiency virus controllers (HICs) form a heterogeneous group of patients with regard to formal definitions, immunologic characteristics, and changes over time in viral load. Patients and Methods The HICs with undetectable viral load ([uHICs] ie, for whom a viral load had never been detected with routine assays; n = 52) were compared with 178 HICs with blips during the follow up (bHICs). Clinical characteristics, ultrasensitive HIV-ribonucleic acid (RNA) and HIV-deoxyribonucleic acid (DNA) loads, HIV1-Western blot profiles, and immune parameters were analyzed. Results Relative to bHICs, uHICs had significantly lower ultrasensitive plasma HIV-RNA loads (P < .0001) and HIV-DNA levels in peripheral blood mononuclear cells (P = .0004), higher CD4+ T-cell count (P = .04) at enrollment, and lower T-cell activation levels. Between diagnosis and inclusion in the cohort, the CD4+ T-cell count had not changed in uHICs but had significantly decreased in bHICs. Twenty-one percent of the uHICs lacked specific anti-HIV immunoglobulin G antibodies, and these individuals also had very low levels of HIV-DNA. Half of the uHICs had a protective human leukocyte antigen (HLA) allele (-B57/58/B27), a weak CD8+ T-cell response, and very small HIV-DNA reservoir. Conclusions We suggest that an interesting HIC phenotype combines protective HLA alleles, low level of HIV blood reservoirs, and reduced immune activation. Prospective studies aimed at evaluating the benefit of combined antiretroviral therapy in HICs might take into account the identification of uHICs and bHICs.

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The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

Current HIV Research ◽

10.2174/1570162x18666200712174642 ◽

2020 ◽

Vol 18 (5) ◽

pp. 354-361

Author(s):

Gülay Okay ◽

Meliha Meric Koc ◽

Eray Metin Guler ◽

Ayşegül Yabaci ◽

Abdürrahim Kocyigit ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Cell Count ◽

Cd4 T Cell ◽

Positive Correlation ◽

Hiv Rna ◽

Tnf Α ◽

Cytokine Levels ◽

Ifn Γ ◽

Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

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Prevalence of Enteric Parasites among HIV Seropositive Patients and Co-Relation with CD4 T Cell Count

International Journal of Current Microbiology and Applied Sciences ◽

10.20546/ijcmas.2016.512.058 ◽

2016 ◽

Vol 5 (12) ◽

pp. 529-537

Author(s):

Nagesh Vithalrao Abdagire ◽

V.V. Chincholkar ◽

S.L. Nilekar ◽

S.R. More

Keyword(s):

T Cell ◽

Cell Count ◽

Cd4 T Cell ◽

Enteric Parasites ◽

Hiv Seropositive ◽

Cd4 T Cell Count

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LB8. Lower SARS-CoV-2 IgG and Pseudovirus Neutralization Titers Post-mRNA Vaccination among People Living with HIV

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1639 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S805-S805

Author(s):

Matthew A Spinelli ◽

Michael J Peluso ◽

Kara Lynch ◽

Cassandra Yun ◽

David V Glidden ◽

...

Keyword(s):

T Cell ◽

Cell Count ◽

Neutralizing Antibody ◽

Cd4 T Cell ◽

People Living With Hiv ◽

Hiv Status ◽

Hiv Rna ◽

Antibody Titers ◽

Adult Medicine ◽

Cd4 T Cell Count

Abstract Background Limited data are available on whether there are differences in the immune response to SARS-CoV-2 vaccination by HIV status or by mRNA vaccine type. Methods We saved residual outpatient laboratory samples of all previously mRNA-vaccinated individuals in the adult medicine clinics of a public hospital with a large outpatient HIV clinic during May 2021, and then excluded individuals with prior SARS-CoV-2 infection. We next 1:1 matched 100 PLWH to 100 outpatient HIV-negative adult medicine patients receiving care for chronic medical conditions on days since completion of second vaccination (minimum 10), sex, age +/-5 years, and the type of mRNA vaccine received. We defined a non-response as reciprocal pseudovirus neutralizing titer< 10 and anti-RBD IgG< 10 relative fluorescent units, and compared non-response by HIV status using mixed models. Results In each matched group there were 13 women; 25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine; the median age was 59. The median time from second vaccination was 35 days (IQR: 20–63). Among PLWH, the median CD4+ T-cell count was 511 (IQR: 351–796) and 5 individuals had HIV RNA > 200. We found 2.4-fold greater odds of pseudovirus neutralizing antibody non-response among PLWH compared to people without HIV (95% CI=1.1–5.4). Although few individuals in each group did not mount an IgG response (12 among PLWH vs. 5; p=0.08), continuous anti-RBD IgG concentrations were 43% lower among PLWH (95% CI=0.36–0.88). Among PLWH, when adjusting for age, sex, and days post-vaccination, each 100-cell increase in CD4+T-cell count was associated with 22% higher neutralizing antibody titers (GMR 1.22; 95% CI=1.09–1.37). Unsuppressed HIV RNA >200 was associated with 89% lower neutralizing antibody titers (GMR 0.11; 95% CI=0.01–0.84). Receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower neutralizing titers (GMR 0.23; 95% CI=0.08–0.65) among PLWH. Post-mRNA Vaccination SARS-CoV-2 IgG Concentrations and Pseudovirus Neutralizing Titers by HIV Status and Vaccine Conclusion PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, with the highest non-response among those with low CD4+ counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Immunization strategies to improve immune responses among PLWH should be studied, and may include booster vaccination or preference of the mRNA-1273 vaccine in this group. Disclosures Matthew A. Spinelli, MD, MAS, Nothing to disclose Monica Gandhi, MD, MPH, Nothing to disclose

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Necrotizing Periodontal Diseases in a Semirural District of South Africa

AIDS Research and Treatment ◽

10.1155/2011/638584 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Neil Hamilton Wood ◽

Elaine Blignaut ◽

Johan Lemmer ◽

Robin Meyerov ◽

Liviu Feller

Keyword(s):

T Cell ◽

Cell Count ◽

Neutrophil Count ◽

Periodontal Diseases ◽

Clinical Signs ◽

Cd4 T Cell ◽

Cell Counts ◽

Hiv Serostatus ◽

Hiv Seropositive ◽

Cd4 T Cell Count

Objectives. The aim of this study was to characterize the lesions of necrotizing gingivitis (NG) and necrotizing periodontitis (NP) with regard to extent and severity, and to correlate these parameters with the host HIV serostatus, CD4+ T-cell count, neutrophil count, age, and gender.Methods. Eighty-four consecutive patients, 39 black females and 45 black males aged 20–46 years, diagnosed with NG/NP were recruited to the study over a period of two years.Results. For both HIV-seropositive and -seronegative patients, the mandibular anterior gingiva was most frequently affected; 74% had NG/NP affecting ≥5 gingival tooth sites. Ninety percent of all patients had a mean severity of ≤4 mm. There was no statistically significant association between either extent or severity of NG/NP and HIV serostatus, CD4+ T-cell count, neutrophil count, age, or gender. The difference between the number of HIV-seropositive patients with NG/NP who had CD4+ T-cell counts ≤200 cells/mm3and those who had CD4+ T cell counts of 201–499 cells/mm3was not statistically significant.Conclusion. The clinical signs of NG/NP are similar in HIV-seropositive and -seronegative patients, and are not related to CD4+ T-cell count, to neutrophil count, to gender, or to age.

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