scholarly journals Broad phenotypic alterations and potential dysfunction of lymphocytes in individuals clinically recovered from COVID-19

2021 ◽  
Author(s):  
Jingyi Yang ◽  
Maohua Zhong ◽  
Ejuan Zhang ◽  
Ke Hong ◽  
Qingyu Yang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cell Subset ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Follicular Helper ◽  
Hla Dr ◽  
Ifn Γ

Abstract Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells (PBMCs) of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor (HD) cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower PD-1 expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM−CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3−HLA-DR− lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B, and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4‒11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that SARS-CoV-2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.

Increased Expression of PD-1 on CD4+ T Cells from Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4154-4154
Author(s):  
Mary M Sartor ◽  
David J Gottlieb
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Effector Memory ◽  
Cd4 Cells ◽  
Normal Peripheral Blood

Abstract Although the predominant finding in patients with chronic lymphocytic leukemia (CLL) is an expansion of monoclonal B lymphocytes, a polyclonal expansion of T cells co-exists in CLL patients. Allogenic stem cell transplants for CLL suggest that a significant graft versus leukaemia effect mediated through recognition of minor MHC or leukaemia specific antigens can be achieved. Since it appears that the immune system and probably T cells recognise CLL cells, it is possible that one or more T cell defects might contribute to the initiation or maintenance of a clone of CLL lymphocytes. PD-1 is a coinhibitory molecule that is expressed on T cells in patients with chronic viral infections. It has been suggested that PD-1 expression might be a marker of cell exhaustion due to antigenic overstimulation. We examined the expression of PD-1 and its naturally occurring ligands PD-L1 and PD-L2 on both B and T cells in patients with CLL and compared this with expression on normal peripheral blood mononuclear cells. We found that PD-1 was expressed on over 10% of CD4+ T cells in 7 of 9 cases of CLL (mean 22±16%) but not on CD4+ T cells in any of 9 normal donors (mean 0±0%), p=0.0009. There was no difference in PD-1 expression on CD8+ or CD14+ PBMCs from CLL patients and normal donors (for CD8+ 24±21% and 19±16% for CLL and normals; for CD14+ 58±16% and 71±31% for CLL and normals). More than 10% of CD5+/19+ CLL cells expressed PD-1 in 7 of 10 cases (mean 18±18%) while more than 10% of normal B cells from 6 of 7 donors also expressed PD-1 (mean 49±30%). We examined the expression of PD-1 on naïve, central memory, effector memory and terminally differentiated subsets of CD4+ cells (CD62L+CD45RA+, CD62L+CD45RA−, CD62L−CD45RA− and CD62L−CD45RA+ respectively) from CLL patients and normal donors. The expression of PD-1 was higher on CD4+ cells from CLL patients in all subsets. The effect was most prominent in the effector memory subset (mean 54±4% for CLL patients versus 26±17% for normal donors, p=0.02). We looked for expression of PD-L1 and PD-L2 on T cells, B cells, monocytes and NK cells from CLL patients and normal donors. PD-L1 was only expressed on monocytes (mean 30±23%) and NK cells (mean 14±19%) from CLL patients and on monocytes from normal donors (mean 35±26%). There was no expression of PD-L2 on any cell type in either CLL patients or normal donors. We conclude that there is increased expression of the co-inhibitory molecule PD-1 on CD4+ T cells in patients with CLL. Ligation of PD-1 by PD-L1 expressed on monocytes or NK cells could inhibit immune responses to tumor and infectious antigens leading to persistence of clonally expanded cells and predisposition to opportunistic pathogens.

scholarly journals Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the Circulation

2009 ◽  
Vol 77 (5) ◽  
pp. 1888-1893 ◽  
Author(s):  
Taufiqur Rahman Bhuiyan ◽  
Samuel B. Lundin ◽  
Ashraful Islam Khan ◽  
Anna Lundgren ◽  
Jason B. Harris ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Vibrio Cholerae ◽  
Mononuclear Cells ◽  
Acute Stage ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Vibrio Cholerae O1 ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-γ) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4+ T cells (CD4+ β7+), gut-homing CD8+ T cells (CD8+ β7+), and gut-homing B cells (CD19+ β7+) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4+ and CD8+ T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-γ responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-γ) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.

scholarly journals Immune Modulation of Platelet-Derived Mitochondria on Memory CD4+ T Cells in Humans

2020 ◽  
Vol 21 (17) ◽  
pp. 6295
Author(s):  
Haibo Yu ◽  
Wei Hu ◽  
Xiang Song ◽  
Yong Zhao
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Effector Memory ◽  
Gene Expressions ◽  
Peripheral Blood Mononuclear ◽  
Immune Modulators ◽  
Cd28 Bead ◽  
Stromal Cell Derived Factor

CD4+ T cells are one of the key immune cells contributing to the immunopathogenesis of type 1 diabetes (T1D). Previous studies have reported that platelet-derived mitochondria suppress the proliferation of peripheral blood mononuclear cells (PBMC). To further characterize the immune modulation of platelet-derived mitochondria, the purified CD4+ T cells were treated, respectively, with platelet-derived mitochondria. The data demonstrated that MitoTracker Deep Red-labeled platelet-derived mitochondria could directly target CD4+ T cells through C-X-C motif chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1 (SDF-1), regulating the anti-CD3/CD28 bead-activated CD4+ T cells. The result was an up-regulation of Naïve and central memory (TCM) CD4+ T cells, the down-regulation of effector memory (TEM) CD4+ T cells, and modulations of cytokine productions and gene expressions. Thus, platelet-derived mitochondria have a translational potential as novel immune modulators to treat T1D and other autoimmune diseases.

scholarly journals Impact of Cryopreservation on Viability, Phenotype, and Functionality of Porcine PBMC

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanli Li ◽  
Enric Mateu ◽  
Ivan Díaz
Keyword(s):  
T Cells ◽  
Cell Viability ◽  
Mononuclear Cells ◽  
Effector Memory ◽  
Respiratory Syndrome Virus ◽  
Double Positive ◽  
Peripheral Blood Mononuclear ◽  
Recall Antigen ◽  
Ifn Γ ◽  
The Impact

The use of frozen peripheral blood mononuclear cells (PBMC) is common in immunological studies. The impact of freezing PBMC has been assessed using human and mice cells, but little information is available regarding domestic animals. In the present study, the phenotype and functionality of frozen porcine PBMC were examined. In a preliminary experiment, three freezing media: fetal bovine serum plus 10% dimethyl sulfoxide, PSC cryopreservation kit, and Cryostor CS10, were compared regarding the preservation of cell viability and the response of PBMC to mitogens after thawing. After being stored one month in liquid nitrogen, cell viability was above 89% for all freezing media. The ELISPOT IFN-gamma (IFN-γ) results in response to PHA and of IgG ELISPOT in response to R848+IL-2 were similar to those obtained using fresh PBMC. In the second set of experiments, PBMC were obtained from five pigs vaccinated against Porcine reproductive and respiratory syndrome virus (PRRSV) and then frozen using Cryostor CS10. Recovered cells were phenotyped by flow cytometry using anti-CD3, CD4, CD8, and CD21 antibodies and were used to assess the PRRSV-specific responses in a proliferation experiment, an IFN-γ ELISPOT, and an IgG ELISPOT, and compared to the results obtained with fresh cells. The antigen-specific responses of frozen cells were significantly (p<0.05) impaired in the proliferation assay, particularly for CD4/CD8 double-positive T-cells and for CD21+ cells. Freezing resulted in decreased proliferation when Con A, but not PHA, was used. In ELISPOT, cryopreservation resulted in a decreased frequency of IFN-γ-secreting cells in response to PRRSV (p<0.05) but the response to PHA was not affected. No differences were observed in the IgG ELISPOT after polyclonal activation. Taken together, cryopreservation of porcine PBMC had a significant impact on the magnitude of recall antigen responses and therefore, it may affect the response of effector/memory cells but seems not to have a major impact on naïve T-cells. These results may help to the better use of frozen porcine PBMC, and to the interpretation of the results obtained from them.

scholarly journals CD4+T cells in ageing-associated interstitial lung abnormalities show evidence of pro-inflammatory phenotypic and functional profile

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215520
Author(s):  
Carlos Machahua ◽  
Ivette Buendia-Roldan ◽  
Ranferi Ocaña-Guzman ◽  
María Molina-Molina ◽  
Annie Pardo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Lung Abnormalities ◽  
Immune Deficiencies

BackgroundInterstitial lung abnormalities (ILA) occur in around 10% of subjects over 60 years, and are associated with a higher rate of all-cause mortality. The pathogenic mechanisms are unclear, and the putative contribution of alterations in the immune response has not been explored. Normal ageing is associated with immune deficiencies, including Naïve T-cell decrease and greater expression of the proliferative-limiting, co-inhibitory receptor killer-cell lectin-like receptor G1 (KLRG1).ObjectiveTo evaluate the frequency and activation state of different T-cell subpopulations in ILA subjects.MethodsPeripheral blood mononuclear cells were obtained from 15 individuals with ILA, 21 age-matched controls and 28 healthy young subjects. T-cells phenotype was characterised by flow cytometry, and proliferation and activation by stimulation with anti-CD3/anti-CD28 or phorbol myristate acetate/ionomycin; KLRG1 isoforms were evaluated by western blot and cytokines were quantified by ELISA and Multiplex.ResultsA significant increase of Naïve CD4+T cells together with a decrease of central and effector memory CD4+T cells was observed in ILA compared with age-matched controls. CD4+T cells from ILA subjects exhibited greater basal proliferation, which raised after anti-CD3/anti-CD28 stimulation. Additionally, a significant increase in the levels of interleukin-6 and interferon gamma was observed in isolated CD4+T cells and plasma of ILA subjects. They also displayed fewer KLRG1+/CD4+T cells with an increase of circulating E-cadherin, the ligand of KLRG1+. No changes were observed with CD8+T cell subsets.ConclusionCD4+T cells from ILA subjects are highly proliferative and show an excessive functional activity, likely related to the loss of KLRG1 expression, which may contribute to an inflammatory state and the development of ILA.

scholarly journals Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy

2019 ◽  
Vol 104 (9) ◽  
pp. 4067-4077 ◽  
Author(s):  
Guo Chen ◽  
Yungang Ding ◽  
Qian Li ◽  
Yanbing Li ◽  
Xiaofeng Wen ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Regulatory B Cells ◽  
Peripheral Blood Mononuclear ◽  
Thyroid Associated Ophthalmopathy ◽  
Ifn Γ

Abstract Purpose To investigate the change in IL-10–producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10–producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays. Results Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro. Conclusions Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.

scholarly journals AB0049 IMMUNE DYSFUNCTION IN ANKYLOSING SPONDYLITIS (AS) AND THE POTENTIAL OF TUMOR NECROSIS FACTOR-Α (TNF-α) INHIBITOR ANBAINUO AS AN EFFECTIVE TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1327.2-1327
Author(s):  
M. Yang ◽  
Q. Lv ◽  
Q. Wei ◽  
J. Gu
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
B Cells ◽  
Immune Function ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Helper T Cells ◽  
Effector Memory ◽  
Follicular Helper

Background:Studies into ankylosing spondylitis (AS) and its relationship with immune function are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune function is unclear.Objectives:We conducted a prospective study of T-cell and B-cell subset distribution and analyzed lymphocyte function in AS patients to further clarify changes to the immune system caused by AS and to explore resistance that could contribute to relapse after treatment.Methods:A total of 40 immune cells were tested with flow cytometry, and the results of 105 HC (healthy control) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of Anbainuo therapy were analyzed.Results:Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (p<0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (p<0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (p<0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (p<0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (p<0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (p<0.001, 0.0001 and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (p<0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (p<0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (p<0.01and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in CRP (C-reactive protein) (r= 0.489, p=0.018).Conclusion:We found that, in terms of both innate and acquired immunity, active-stage AS patients have an immunity imbalance involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. Anbainuo can not only help to inhibit disease activity and partial immune function imbalance in AS but can also increase the number of negative regulatory cells in inflammation.References:[1]Long, S., et al., High frequency of circulating follicular helper T cells is correlated with B cell subtypes in patients with ankylosing spondylitis. Exp Ther Med, 2018. 15(5): p. 4578-4586.[2]An, H., et al., The absolute counts of peripheral T lymphocyte subsets in patient with ankylosing spondylitis and the effect of low-dose interleukin-2. Medicine (Baltimore), 2019. 98(15): p. e15094.Acknowledgments:Thanks to Professor Zhinan Yin for his support and assistance with this studyDisclosure of Interests:None declared

Perforin Expressing CD4+T Cells Respond to CMV Antigens in CMV Seropositive Patients with B Cell Chronic Lymphocytic Leukaemia (B-CLL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4787-4787
Author(s):  
James Walton ◽  
Keirissa Lawson ◽  
Maria S. Manoussaka ◽  
Amit Nathwani ◽  
Vincent Emory ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cell Subset ◽  
Free Cell ◽  
Strong Increase ◽  
Cell Lysates ◽  
Cd69 Expression ◽  
Ifn Γ

Abstract Introduction: Perforin (PF) expressing CD4+ T cells are expanded in B-CLL patients [1] and are able to induce PF-mediated apoptosis of autologous leukaemic cells in the presence of bispecific anti-CD3/CD19 antibodies [2]. However, the role of the expanded PF+CD4+ T population in B-CLL remains unclear. In this study we have examined possible involvement of this cell subset in immune responses to cytomegalovirus (CMV). Methods: Blood mononuclear cells from 11 CMV seropositive (SP) and 6 seronegative (SN) B-CLL patients were cultured for 4 and 18 hours in presence of Downe cell lysates containing CMV-antigen or cell lysates alone (control) and brefeldin and co-stimulated with anti-CD28 and anti-CD49 monoclonal antibodies. Anti-CMV response was assessed by flow cytometry as percentages of CD69+ and IFNγ+ cells in PF+ and PF- CD4+T cell populations. Results: CD4+ T cells from 9 of 11 SP patients showed a strong increase in percentages of IFNγ+ cells after 18h, but not 4h, in culture with CMV antigens, compared to the control lysates and SN patients (Table) and healthy age-matched SP subjects (1.78±0.45, p=0.012). In contrast, none of the 6 SN patients as well as 2 out of 11 SP patients responded to CMV by increased IFNγ expression. In responders IFNγ+ cells were proportionally distributed between PF+ and PF- CD4+ T cells. High levels of cell activation measured by CD69 expression, especially in PF+ population, were mainly due to the Downe cell lysate since expression was significantly lower in lysate free cell cultures (8.3±11.5%, p=0.0018 for SP B-CLL patients). Anti-CMV response was accompanied by a decrease in percentages of CD4+PF+ cells suggesting antigen-induced degranulation. Conclusion: PF+CD4+ T cells respond to CMV antigens suggesting an expansion of mature CMV specific cytotoxic CD4+ T cells in the majority of CMV seropositive B-CLL patients. IFN-γ and CD69 expression by CD4+PF+ and PF- T cells after 18h exposure to CMV+ and CMV- lysates in CMV seropositive and seronegative B-CLL patients CD4+ PF+ CD4+ PF-CD4+ SN SP SN SP SN SP IFN- γ, % CMV+lys 0.7±0.58 9.1±7.9 2.0±3.0 p=0.013 14.4±13.6 0.61±0.56 p=0.008 9.0±8.1 CMV−lys 0.26±0.34 0.9±1.7 p=0.007 1.1±1.7 3.9±6.9 p=0.029 0.24±0.27 1.46±2.55 p=0.013 CD69+cells, % CMV+lys 16.3±14.2 21.4±13.0 41.9±35.1 51.2±30.3 14.9±13.4 20.4±13.2 CMV−lys 14.4±12.8 9.7±7.8 28.6±34.8 39.8±33.0 13.8±12.1 12.9±15.0

scholarly journals Immune Phenotype and Functionality of Mtb-Specific T-Cells in HIV/TB Co-Infected Patients on Antiretroviral Treatment

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 180 ◽  
Author(s):  
Lucy Mupfumi ◽  
Cheleka A.M. Mpande ◽  
Tim Reid ◽  
Sikhulile Moyo ◽  
Sanghyuk S. Shin ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
High Specificity ◽  
Effector Memory ◽  
Hiv Status ◽  
Roc Curve Analysis ◽  
Immune Phenotype ◽  
Hla Dr ◽  
Latent Tb ◽  
Ifn Γ

The performance of host blood-based biomarkers for tuberculosis (TB) in HIV-infected patients on antiretroviral therapy (ART) has not been fully assessed. We evaluated the immune phenotype and functionality of antigen-specific T-cell responses in HIV positive (+) participants with TB (n = 12) compared to HIV negative (−) participants with either TB (n = 9) or latent TB infection (LTBI) (n = 9). We show that the cytokine profile of Mtb-specific CD4+ T-cells in participants with TB, regardless of HIV status, was predominantly single IFN-γ or dual IFN-γ/ TNFα. Whilst ESAT-6/CFP-10 responding T-cells were predominantly of an effector memory (CD27−CD45RA−CCR7−) profile, HIV-specific T-cells were mainly of a central (CD27+CD45RA−CCR7+) and transitional memory (CD27+CD45RA+/−CCR7−) phenotype on both CD4+ and CD8+ T-cells. Using receiving operating characteristic (ROC) curve analysis, co-expression of CD38 and HLA-DR on ESAT-6/CFP-10 responding total cytokine-producing CD4+ T-cells had a high sensitivity for discriminating HIV+TB (100%, 95% CI 70–100) and HIV−TB (100%, 95% CI 70–100) from latent TB with high specificity (100%, 95% CI 68–100 for HIV−TB) at a cut-off value of 5% and 13%, respectively. TB treatment reduced the proportion of Mtb-specific total cytokine+CD38+HLA-DR+ CD4+ T-cells only in HIV−TB (p = 0.001). Our results suggest that co-expression of CD38 and HLA-DR on Mtb-specific CD4+ T-cells could serve as a TB diagnosis tool regardless of HIV status.

scholarly journals Expansion and Productive HIV-1 Infection of Foxp3 Positive CD4 T Cells at Pleural Sites of Hiv/Tb Co-Infection

2016 ◽  
Vol 1 (1) ◽  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cell Entry ◽  
Cellular Activation ◽  
Hla Dr ◽  
Intracellular Expression ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Strong Stop

Backgrounds: CD4 T-cells expressing Foxp3 are expanded systemically during active tuberculosis (TB) regardless of HIV-1 co-infection. Foxp3+ CD4 T cells are targets of HIV-1 infection. However, expansion of HIV-1 infected Foxp3+ CD4 T cells at sites of HIV/TB co-infection, and whether they contribute to promotion of HIV-1 viral activity is not known. Methods: Pleural fluid mononuclear cells (PFMC) from HIV/TB co-infected patients with pleural TB were characterized by immune-staining and FACS analysis for surface markers CD4, CD127, CCR5, CXCR4, HLA-DR and intracellular expression of Foxp3, HIVp24, IFN-γ and Bcl-2. Whole PFMC and bead separated CD4+CD25+CD127- T cells were assessed for HIV-1 LTR strong stop (SS) DNA by real-time PCR, which represents viral DNA post cell entry and initiation of reverse transcription. Results: High numbers of HIV-1 p24 positive Foxp3+ and Foxp3+CD127– CD4 T cells were identified in PFMC from HIV/TB co-infected subjects. CD4+Foxp3+CD127– T cells displayed high expression of the cellular activation marker, HLA-DR. Further, expression of the HIV-1 co-receptors, CCR5 and CXCR4, were higher on CD4+Foxp3+T cells compared to CD4+Foxp3- T cells. Purified CD4+CD25+CD127– T cells isolated from PFMC of HIV/TB co-infected patients, were over 90% CD4+Foxp3+T cells, and exhibited higher HIV-1 SS DNA as compared to whole PFMC, and as compared to CD4+CD25+CD127– T cells from an HIV-infected subject with pleural mesothelioma. HIV-1 p24+ Foxp3+ CD4+T cells from HIV/TB patients higher in Bcl-2 expression as compared to both HIV-1 p24+ Foxp3- CD4 T cells, and Foxp3+ CD4+T cells without HIV-p24 expression. Conclusion: Foxp3+ CD4 T cells in PFMC from HIV/TB co-infected subjects are predisposed to productive HIV-1 infection and have survival advantage as compared to Foxp3 negative CD4 T cells.

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