CD8 T cells from HIV positive individuals on ART have a skewed differentiation phenotype and impaired proliferative responses

To determine the correlates of immune recovery from active human CMV (HCMV) disease, we compared the antigenic repertoire, diversity, magnitude, and differentiation of HCMV-specific CD8+ T cells in HIV-HCMV coinfected subjects with no, cured, or active HCMV disease and in healthy HIV-negative HCMV-positive controls. ELISPOT–IFN-γ assays using peptide pools spanning the pp65 and immediate early 1 (IE1) HCMV proteins showed that HCMV-specific CD8+ T cells had a significantly broader antigenic repertoire and greater diversity in HIV-positive patients controlling HCMV replication than in those with active HCMV disease, but the magnitude of the CD8 T cell response did not differ between the different groups. HCMV-specific T cells mainly were focused against IE1 during the short-term recovery from retinitis, and switched toward pp65 during long-term recovery. HCMV-specific T cells displaying an “early” (CD8+CD27+CD28+) and “intermediate” (CD8+CD27−CD28+) differentiation phenotype were increased significantly during long-term recovery compared with other HIV-positive patients and were nearly undetectable during active HCMV disease. HCMV-specific T cells with a “late” (CD8+CD27−28−) differentiation phenotype predominated in all cases. Therefore, restoration of immune protection against HCMV after active HCMV disease in immunodeficient individuals is associated with enlarged repertoire and diversity, and with early differentiation of virus-specific CD8+ T cells, thus defining immune correlates of protection against diseases caused by persistent viruses.

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Correlation of Immune Activation during Late Pregnancy and Early Postpartum with Increases in Plasma HIV RNA, CD4/CD8 T Cells, and Serum Activation Markers

Clinical and Vaccine Immunology ◽

10.1128/cvi.00088-10 ◽

2010 ◽

Vol 17 (12) ◽

pp. 2024-2028 ◽

Cited By ~ 12

Author(s):

Hong-Ha M. Truong ◽

Myung S. Sim ◽

Maryanne Dillon ◽

Christel H. Uittenbogaart ◽

Ruth Dickover ◽

...

Keyword(s):

T Cells ◽

Pregnant Women ◽

Cd8 T Cells ◽

Immune Activation ◽

Hiv Positive ◽

Third Trimester ◽

Β2 Microglobulin ◽

Hiv Rna ◽

The Third ◽

Hiv Negative

ABSTRACT A previously observed rise in the plasma viral load postpartum in both treated and untreated HIV-positive women remains unexplained. Virological and immunological markers were evaluated in HIV-negative controls and HIV-positive pregnant women with and without antiretroviral treatment. Plasma HIV RNA, CD4/CD8 T cells, and serum activation markers were sequentially measured during the third trimester, at delivery, and 2 to 8 weeks postpartum in a cohort of HIV-positive pregnant women (n = 96) enrolled in a maternal-fetal HIV transmission study and a control group of HIV-negative pregnant women (n = 28). Mean plasma HIV RNA (P = 0.003) increased from delivery to postpartum, and mean CD4 T cells (P = 0.002) and serum β2-microglobulin (P < 0.0001) increased from the third trimester through postpartum among the HIV-positive women. Mean CD8 T cells increased from the third trimester through postpartum in women receiving zidovudine (ZDV) and in those not treated (P < 0.05) but remained stable in those on highly active antiretroviral therapy (HAART) and the HIV-negative controls. Increases in serum β2-microglobulin were correlated with increases in HIV RNA (P = 0.01). HIV-positive pregnant women showed postpartum increases in plasma HIV RNA, CD4 T cells, and serum β2-microglobulin regardless of the treatment regimen. The rise in CD4 T cells and β2-microglobulin was also observed in HIV-negative pregnant women, suggesting hormonal changes and/or labor-induced cytokines may contribute to immune activation. Immune activation correlated with increased plasma HIV RNA in postpartum women despite treatment, although HAART appeared to blunt the effect. The observed rise in plasma HIV RNA postpartum, which correlated with markers of immune activation, may have implications for enhanced transmission to infants through early breast-feeding and to sexual partners.

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Expansion of pre-terminally differentiated CD8 T cells in chronic HIV-positive patients presenting a rapid viral rebound during structured treatment interruption

AIDS ◽

10.1097/00002030-200212060-00008 ◽

2002 ◽

Vol 16 (18) ◽

pp. 2431-2438 ◽

Cited By ~ 23

Author(s):

Gianpiero D'Offizi ◽

Carla Montesano ◽

Chiara Agrati ◽

Cristiana Gioia ◽

Massimo Amicosante ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Treatment Interruption ◽

Hiv Positive ◽

Viral Rebound

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Role ofIn VitroStimulation with Lipopolysaccharide on T-Cell Activation in HIV-Infected Antiretroviral-Treated Patients

Clinical and Developmental Immunology ◽

10.1155/2012/935425 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Camilla Tincati ◽

Giusi M. Bellistrì ◽

Giuseppe Ancona ◽

Esther Merlini ◽

Antonella d’Arminio Monforte ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cd8 T Cells ◽

Cell Activation ◽

Hiv Positive ◽

Cd38 Expression ◽

Hla Dr ◽

Measured Flow

We investigated the effect of LPSin vitrostimulation on T-cell activation in HIV-infected patients with different CD4+ recovery on HAART. PBMCs from 30 HIV-positive, HAART-treated, aviremic individuals with different CD4+ reconstitution (Low Responders: CD4+ < 350/μL; Intermediate Responders: CD4+ 350–599/μL; High Responders: CD4+ ≥ 600/μL) were cultured with LPS and the proportion of HLA-DR/CD38- and Ki67-expressing CD4+/CD8+ T-cells was measured (flow cytometry). Upon LPS stimulation, significantly higher CD4+ and CD8+HLA-DR+ cells were shown in LR and IR versus HIV-negative controls. While no differences in the proportion of LPS-stimulated CD4+CD38+ cells were recorded amongst HIV-positive subgroups, CD8+CD38+ cells were more elevated in patients with lower CD4+ recovery on HAART (i.e., LR and IR). Uponin vitroLPS stimulation, HLA-DR and CD38 expression on T-cells are differentially regulated. While HLA-DR induction reflects impaired CD4+ reconstitution on HAART, cell-surface CD38 expression is increased only on CD8+ T-cells, allowing to speculate that the sole induction of CD38 on CD4+ cells may not be sufficient to depict LPS-driven immune activation in HIV.

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Diminished CD103 (aEb7) Expression on Resident T cells from the Female Genital Tract of HIV-positive women

Pathogens and Immunity ◽

10.20411/pai.v1i2.166 ◽

2017 ◽

Vol 1 (2) ◽

pp. 371 ◽

Cited By ~ 13

Author(s):

David C. Moylan ◽

Paul A. Goepfert ◽

Mirjam-Colette Kempf ◽

Michael S. Saag ◽

Holly E. Richter ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Genital Tract ◽

Female Genital Tract ◽

Hiv Positive ◽

Hiv Positive Women ◽

Mucosal Surfaces ◽

Polychromatic Flow Cytometry ◽

Female Genital

Background:Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT).Methods: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103+CD69+ CD4+ and CD8+ T cells in mucosa-derived T cells from healthy and HIV-positive women.Results: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women. The expression of the mucosal retention receptor, CD103, from HIV-positive women was reduced compared to healthy women and was lowest in women with CD4 counts < 500 cells/mm3. Furthermore, CD103 expression on mucosa-derived CD8+ T cells correlated with antigen-specific IFN-γ production by mucosal CD4+ T cells and was inversely correlated with T-bet from CD8+CD103+ mucosa-derived T cells.Conclusions: These data suggest that CD4+ T cells, known to be impaired during HIV-1 infection and necessary for the expression of CD103 in murine models, may play a role in the expression of CD103 on resident T cells from the human FGT.

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Altered Expression of PYCARD, Interleukin 1β, Interleukin 18, and NAIP in Successfully Treated HIV-Positive Patients With a Low Ratio of CD4+ to CD8+ T Cells

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy730 ◽

2019 ◽

Vol 219 (11) ◽

pp. 1743-1748 ◽

Cited By ~ 3

Author(s):

Milena Nasi ◽

Simone Pecorini ◽

Sara De Biasi ◽

Elena Bianchini ◽

Margherita Digaetano ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Interleukin 1Β ◽

Hiv Positive ◽

Interleukin 18 ◽

Altered Expression

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Comparative Evaluation of the Levels of CD4+ and CD8+ T-Cells, Viral Load, and Some Immunomodulatory Trace Elements in ART and ART-naïve HIV Patients in Port-Harcourt, Nigeria

Asian Journal of Medicine and Health ◽

10.9734/ajmah/2021/v19i930374 ◽

2021 ◽

pp. 127-133

Author(s):

Ugochukwu Chioma ◽

Helen Anthony Waribo ◽

Donatus O. Onwuli

Keyword(s):

T Cells ◽

Trace Elements ◽

Viral Load ◽

T Cell ◽

Cd8 T Cells ◽

Venous Blood ◽

Cd4 T Cell ◽

Hiv Positive ◽

Port Harcourt ◽

The Mean

Aim: To evaluate the levels of CD4+ and CD8+ T-cells, viral load, and some immunomodulatory trace elements in ART and ART-naïve HIV patients in Port-Harcourt, Nigeria. Methodology: A total of 150 subjects (males and females) between the ages of 20 and 79 were recruited for the study, out of which 50 subjects were apparently healthy (those who tested negative for HIV), and were used as the control group, while the remaining 100 subjects were those who tested positive for HIV, and were used as the test group; out of this 100 subjects, 70 subjects were on anti-retroviral therapy (ART), while the remaining 30 subjects were not on anti-retroviral therapy (ART naïve). About 13 mls of venous blood was collected from the antecubital fossa of each subject. 3mls was dispensed into an EDTA-anticoagulant bottle, and used for the estimation of CD4+ and CD8+ counts using a BD fluorescent activated cell sorter count (FACSC count) automation. Also, 5mls of the venous blood was dispensed into another EDTA-anticoagulated bottle; it was spun to obtain the plasma which was used to analyze the viral load using real time polymerase chain reaction (RT-PCR) COBAS TaqMan 48 Analyzer. Then, another 5 mls of the venous blood was dispensed into lithium heparin bottle; it was spun to obtain the plasma, which was used for the analysis of copper, iron, zinc and magnesium by colorimetric method using semi auto-analyzer WP 21E, and selenium using atomic absorption spectrophotometer with graphite furnace technique SN-SG 710690. Results: The results showed that there was no significant difference (p>0.05) in the mean levels of CD8+ T-cell, iron and magnesium between the HIV-positive subjects (ART HIV-positive and ART-naïve HIV-positive) and the control. However, the mean levels of CD4+ T-cell and plasma copper were significantly lower (p<0.05) in the HIV-positive subjects compared to the control; also, the mean levels of the CD4+ T-cell in the ART-naïve subjects were significantly lower compared to the ART subjects. The viral load in ART-naïve subjects were significantly higher compared to the ART subjects and control. However, the mean levels of zinc and selenium were significantly lower in the HIV-positive subjects compared to the control. Conclusion: Based on these results, it may be stated that some immunomodulatory trace elements such as zinc and selenium were deficient in HIV-positive subjects, and as such, addition of zinc and/or selenium supplements in the treatment regimen for HIV-positive subjects may be helpful in boosting their immunity and effective management.

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