scholarly journals In Situ Activation of Helper T Cells in the Lung

2001 ◽  
Vol 69 (8) ◽  
pp. 4790-4798 ◽  
Author(s):  
Bindu Raju ◽  
Chung F. Tung ◽  
Debbie Cheng ◽  
Nora Yousefzadeh ◽  
Rany Condos ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Cell Marker ◽  
Color Flow ◽  
Purified Protein Derivative ◽  
Surface Molecules ◽  
In Situ Activation ◽  
Significant Difference

ABSTRACT To better understand the lung and systemic responses of helper T cells mediating memory immunity to Mycobacterium tuberculosis, we used three- and four-color flow cytometry to study the surface phenotype of CD4+ lymphocytes. Bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) samples were obtained from a total of 25 subjects, including 10 tuberculosis (TB)-infected subjects, 8 purified-protein-derivative-negative subjects, and 7 purified-protein-derivative-positive subjects. In marked contrast to CD4+ lymphocytes from PB (9% ± 5% expressing CD45RA and CD29), the majority (55% ± 16%) of CD4+ lymphocytes in BAL (ALs) simultaneously expressed CD45RA, a naı̈ve T-cell marker, and CD29, members of the very late activation family. Further evaluation revealed that CD4+ ALs expressed both CD45RA and CD45RO, a memory T-cell marker. In addition, the proportion of CD4+ lymphocytes expressing CD69, an early activation marker, was drastically increased in BAL fluid (83% ± 9%) compared to PB (1% ± 1%), whereas no significant difference was seen in the expression of CD25, the low-affinity interleukin 2 receptor (34% ± 15% versus 40% ± 16%). More importantly, we identified a minor population of CD69bright CD25bright CD4+lymphocytes in BAL (10% ± 6%) that were consistently absent from PB (1% ± 1%). Thus, CD4+ lymphocytes in the lung paradoxically coexpress surface molecules characteristic of naı̈ve and memory helper T cells as well as surface molecules commonly associated with early and late stages of activation. No difference was observed for ALs obtained from TB-infected and uninfected lung segments in this regard. It remains to be determined if these surface molecules are induced by the alveolar environment or if CD4+ lymphocytes coexpressing this unusual combination of surface molecules are selectively recruited from the circulation. Our data suggest that ex vivo experiments on helper T-cell subsets that display distinctive phenotypes may be pivotal to studies on the human immune response to potential TB vaccines.

6 Murine T cell subsets and interleukins: Relationships between cytotoxic T cells, helper T cells and accessory cells

1982 ◽  
Vol 11 (3) ◽  
pp. 607-630
Author(s):  
Hermann Wagner ◽  
Martin Kronke ◽  
Werner Solbach ◽  
Peter Scheurich ◽  
Martin Röllinghoff ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Accessory Cells

scholarly journals Pomalidomide Induces Expansion of Activated and Central Memory CD4+ and CD8+ T Cells in Vivo in Patients with and without HIV Infection

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4128-4128 ◽  
Author(s):  
Mark N. Polizzotto ◽  
Irini Sereti ◽  
Thomas S. Uldrick ◽  
Kathleen M. Wyvill ◽  
Stig M. R. Jensen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Research Funding ◽  
Kaposi Sarcoma ◽  
Central Memory ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Significant Difference

Abstract Background: Despite antiretroviral therapy (ART), people with HIV continue to exhibit immune deficits including failure to fully reconstitute CD4 T cell numbers and function, resulting in increased risks of tumors and infections and reduced response to vaccination. Pomalidomide, a derivative of thalidomide (IMID), has immunomodulatory properties that may be beneficial in this setting. We explored its impact on lymphocyte number and activation in patients with and without HIV treated within a prospective clinical trial for Kaposi sarcoma. Methods: Patients received pomalidomide 5mg orally for 21 days of 28 day cycles. Assessments were performed every 4 weeks for lymphocyte numbers, Kaposi sarcoma associated herpesvirus (KSHV/HHV8) viral load (VL) and HIV VL and at 8 weeks for T cell subsets and activation by immunophenotyping of peripheral blood mononuclear cells (PBMC). KSHV VL in PBMC and HIV VL in plasma were assayed by quantitative PCR; for HIV VL we used an ultrasensitive single copy assay. Changes from baseline were evaluated using the Wilcoxon signed rank test with P<0.005 considered significant given multiple comparisons. Differences in changes between the HIV infected and uninfected groups were evaluated using the Wilcoxon rank sum test. Study registered as NCT1495598. Results: 19 patients (12 HIV infected, 7 uninfected) median age 50 years (range 32-74) were studied. All with HIV were receiving ART for median 48 months (7-227), HIV VL 1.5 copies/mL (<0.5–37), and CD4 378 cells/µl (135–752). At week 4 and 8 of therapy we observed significant increases in CD4 and CD8 counts, with a decline in CD19 B cells and no change in NK cells or HIV VL. A transient increase in KSHV VL was seen at week 4, not sustained at week 8: Abstract 4128. Table 1ParameterBaseline (cells/µl unless noted)Change to Week 4 (Med, range)PChange to Week 8 (Med, range)PCD31143 (525–2305)+264 (-419–1524)0.0028+210 (-496–1455)0.0020CD4429 (135–1171)+107 (-87–650)0.0009+86 (-37–491)0.0015CD8495 (259–1529)+108 (-271–915)0.0085+155 (-495–834)0.0046NK184 (28–557)+30 (-130–117)0.52+2 (-174–127)0.98CD19139 (9–322)-47 (-117–76)0.0039-79 (-169–62)<0.0001KSHV VL 0 copies/PBMC (0–8750)+23 (-92–5250)0.00980 (-92–20850)0.31Plasma HIV VL (infected pts)1.5 copies/mL (<0.5–37)+0.3 (-1.5–3.0)0.75+0.75 (0–28)0.13 In addition, at week 8 both CD4 and CD8 T cells showed significant increases in activation (CD38+, HLADR+ and DR+/38+) and decreases in senescence (CD57+). Both also showed a significant shift towards increased central memory (CM) and away from naive (N) and effector (E) phenotypes, with no change in effector memory (EM) cells: Abstract 4128. Table 2CD4 SubsetsBaseline (%) (med, range)Absolute Change in % at Week 8 (med, range)PRO- 27+ (N)32.6 (13.3–76.5)-6.6 (-35.8–21.6)0.002RO+ 27+ (CM)41.9 (13.6–63.6)+6.4 (-15.5–32.5)0.027RO+ 27- (EM)16.7 (4.6–31.7)+1.7 (-7.2–21.0)0.28RO- 27- (E)3.3 (0.4–14.3)-1.5 (-5.7–0.3)0.000438+34.5 (11.2–67.3)+4.3 (-13.0–19.4)0.024HLA DR+8.9 (3.3–25.0)+8.3 (0.7–19.5)<0.000138+ DR+2.5 (0.6–11.7)+2 (-1.0–8.1)<0.000157+6.3 (0.6–26.6)-1.34 (-16.2–7.6)0.034CD8 SubsetsRO- 27+ (N)21.0 (9.7–70.4)-5.1 (-13.7–14.3)0.019RO+ 27+ (CM)17.1 (2.5–37.9)+8.1 (-8.4–18.6)0.0047RO+ 27- (EM)18.4 (4.6–40.8)+1.0 (-9.4–44.9)0.35RO- 27- (E)31.8 (4.1-63.7)-6.1 (-47.3–22.5)0.0138+33.4 (8.3–66.0)+19.9 (-0.8–40.6)<0.0001HLA DR+19.6 (5.0–46.4)+11.6 (-4.7–32.1)0.000138+ DR+8.0 (0.4–33.3)+8.5 (0.1–22.6)<0.000157+30.8 (2.9–72.9)-11.0 (-28.5–6.1)<0.0001 There were no significant changes in Ki67 or PD-1 expression in either CD4 or CD8 cells. There was no significant difference between HIV infected and uninfected patient groups in the observed effects on any parameter including cell number and phenotype. Conclusions: Pomalidomide induced significant increases in the number of CD4 and CD8 T cells and the proportion of activated and central memory cells and decreased senescence in both HIV infected and uninfected subjects. Effects were not explained by alterations in HIV viremia. The transient early rise in KSHV VL may reflect reactivation of latent infection and enhance immune killing of KSHV infected cells. This analysis sheds light on possible mechanisms of IMID activity in viral-associated tumors. As the first study of immune modulation by IMIDs in vivo in people with HIV it also suggests exploration of IMIDs to augment immune responsiveness in HIV and other immunodeficiencies is warranted. Disclosures Polizzotto: Celgene Corporation: Research Funding. Off Label Use: Pomalidomide for Kaposi sarcoma. Uldrick:Celgene Corporation: Research Funding. Zeldis:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Yarchoan:Celgene Corporation: Research Funding.

scholarly journals Characterization of CD4-Positive Lymphocytes in the Antiviral Response of Olive Flounder (Paralichthys oliveceus) to Nervous Necrosis Virus

2020 ◽  
Vol 21 (11) ◽  
pp. 4180
Author(s):  
Jae Wook Jung ◽  
Jin Hong Chun ◽  
Jung Seok Lee ◽  
Si Won Kim ◽  
Ae Rin Lee ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Viral Infection ◽  
T Cell Subsets ◽  
Olive Flounder ◽  
Flow Cytometry Analysis ◽  
Color Flow

The presence of CD4 T lymphocytes has been described for several teleost species, while many of the main T cell subsets have not been characterized at a cellular level, because of a lack of suitable tools for their identification, e.g., monoclonal antibodies (mAbs) against cell markers. We previously described the tissue distribution and immune response related to CD3ε and CD4-1 T cells in olive flounder (Paralichthys oliveceus) in response to a viral infection. In the present study, we successfully produce an mAb against CD4-2 T lymphocytes from olive flounder and confirmed its specificity using immuno-blotting, immunofluorescence staining, flow cytometry analysis and reverse transcription polymerase chain reaction (RT-PCR). Using these mAbs, we were able to demonstrate that the CD3ε T cell populations contain both types of CD4+ cells, with the majority of the CD4 T cell subpopulations being CD4-1+/CD4-2+ cells, determined using two-color flow cytometry analysis. We also examined the functional activity of the CD4-1 and CD4-2 cells in vivo in response to a viral infection, with the numbers of both types of CD4 T cells increasing significantly during the virus infection. Collectively, these findings suggest that the CD4 T lymphocytes in olive flounder are equivalent to the helper T cells in mammals in terms of their properties and function, and it is the CD4-2 T lymphocytes rather than the CD4-1 T cells that play an important role in the Th1 immune response against viral infections in olive flounder.

scholarly journals Cytotoxic CD8+ T Cells Expressing CXCR5 Are Detectable in HIV-1 Elite Controllers After Prolonged In Vitro Peptide Stimulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Philipp Adams ◽  
Gilles Iserentant ◽  
Jean-Yves Servais ◽  
Linos Vandekerckhove ◽  
Guido Vanham ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Color Flow ◽  
Cell Immunity ◽  
Ifn Γ ◽  
Peptide Stimulation ◽  
Hiv Controllers ◽  
Hiv 1

Antiretroviral therapy (ART) is not curative as HIV-1 persists in long-lived viral reservoirs. Consequently, patients are dependent on life-long drug adherence with possible side effects. To overcome these limitations strategies of a functional cure aim at ART free viral remission. In this study, we sought to identify detailed subsets of anti-viral CD8+ T cell immunity linked to natural long-term control of HIV-1 infection. Here, we analyzed HIV controllers and ART suppressed progressors for in vitro viral suppressive capacity (VSC) at baseline and after peptide stimulation. Functional properties and phenotypes of CD8+ T cells were assessed by IFN-γ ELISPOT and 18 color flow cytometry. HIV controllers showed significantly increased suppression at baseline as well as after peptide stimulation. IFN-γ secretion and the proliferation marker Ki67 positively correlated with VSC. Moreover, the detailed phenotype of three distinct multifunctional memory CD8+ T cell subsets were specific traits of HIV controllers of which two correlated convincingly with VSC. Our results underline the importance of multifunctional CD8+ T cell responses during natural control. Especially the role of CXCR5 expressing cytotoxic subsets emphasizes potential surveillance in sites of reservoir persistence and demand further study.

scholarly journals Up-regulated Expression of Fas Antigen in Peripheral T cell Subsets in Patients with Myasthenia Gravis

2012 ◽  
Vol 35 (5) ◽  
pp. 294 ◽  
Author(s):  
Weihua Mai ◽  
Xingwei Liu ◽  
Yunping Fan ◽  
Hanwei Liu ◽  
Hai Yu Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Myasthenia Gravis ◽  
Cd8 T Cells ◽  
Corticosteroid Treatment ◽  
T Cell Subsets ◽  
Chinese Patients ◽  
Fas Antigen ◽  
Significant Difference ◽  
Regulated Expression

Purpose: Recent reports have linked various autoimmune diseases to defective Fas-mediated apoptosis or Fas expression. Here we aimed to determine whether Fas-mediated apoptosis is involved in the pathogenesis of myasthenia gravis (MG). Methods: The expression of Fas antigen in peripheral T cell subsets from 17 Chinese patients with MG and 13 healthy individuals was determined by flow cytometry, and its associations with clinical classification, thymus pathology, the concomitance with hyperthyroidism (HT) and corticosteroid treatment were investigated. Results: Compared with normal controls, a significantly up-regulated expression of Fas antigen was observed in the peripheral CD4+, CD4+CD8- and CD4-CD8- T cell subsets from patients with MG. Fas expression in CD4-CD8+ T cells of MG patients with normal thymus was significantly higher than that of patients with thymoma. Fas expressions in CD4+CD8+ T cells in MG patients with HT was significantly higher than controls and the ones without HT. Enhanced Fas expressions was found in CD4-CD8+ and CD4-CD8- T cells of MG patients with corticosteroid treatment, but no significant difference of Fas expression in peripheral T cells between patients with ocular MG (OMG) and general MG (GMG) was observed. Conclusion: Fas antigen may play a role in the pathogenesis of MG. It may be involved in the mechanisms of corticosteroid treatment, and with the occurrence of HT. OMG may represent a systemic disease, similar to that of GMG.

scholarly journals CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer

2020 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Color Flow ◽  
Draining Lymph Nodes

Abstract Background: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8+ memory T cell subsets including stem memory T cells (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC). Methods: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8+ lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software. Results: We observed that 47.65±2.66% of CD8+ lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P=0.024 and P=0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45ROhi and CD45ROlow subsets, and TSCM was higher in patients with stage II compared to those in stage I (P<0.05). In addition, the percentage of naive CD8+ T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P=0.025). Conclusions: Our data collectively indicate no significant differences in the frequencies of CD8+ lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45low TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45low TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells’ differentiation (CD45ROlow), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.

Effect of 2,3,7,8-Tetrachloro-di-benzo-p-dioxin on T Cell Subpopulations in the Thymus and Spleen of Mice with Chronic Toxoplasma gondii Infection

2000 ◽  
Vol 19 (5) ◽  
pp. 323-329 ◽  
Author(s):  
Marquea D. King ◽  
David S. Lindsay ◽  
Marion F. Ehrich ◽  
Mitzi Nagarkatti
Keyword(s):  
T Cells ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
Cd8 T Cells ◽  
Brain Lesion ◽  
Environmental Pollutant ◽  
T Cell Subsets ◽  
Double Positive ◽  
Significant Difference ◽  
Tcdd Treatment

In the current study, the effect of exposure to the environmental pollutant, 2,3,7,8-tetrachloro-di-benzo- p-dioxin (TCDD), on mice having chronic infection with Toxoplasma gondii was investigated. For this purpose, four groups of mice were used—mice treated with vehicle, mice treated with TCDD alone, mice infected with T. gondii alone, and mice receiving a combination of TCDD treatment and T. gondii infection. Histological examination and tissue cyst enumeration were performed to indicate the level of infection of the brain. The immune status was studied by enumerating the cellularity as well as the percentages and absolute numbers of the lymphocyte subsets based on the expression of CD4 and CD8 markers in the thymus and spleen. Our studies demonstrated that there was a significant decrease in the total number of thymocytes in TCDD-treated mice that were either uninfected or infected with T. gondii when compared to vehicle controls. However, there was no significant difference observed in thymic cellularity in mice that were infected with T. gondii alone when compared to the uninfected vehicle controls. In addition, the ratio and the total numbers of CD4+, CD8+, CD4–CD8–(double negative, DN) and CD4+CD8+ (double positive, DP) T cell subsets in the thymus from various groups were determined. There was no change in the percentages of T cell subsets in TCDD-treated mice or T. gondii-infected mice when compared to the vehicle controls. However, there was a decrease in the percentage of DPT cells and an increase in the DN and CD8+ T cells in mice that received a combination of TCDD-treatment and T. gondii infection when compared to mice receiving the vehicle or TCDD-treatment alone or infection with T. gondii alone. There was also a decrease in the absolute numbers of the DP and CD4+ T cells and an increase in the CD8+ T cells in the thymus of mice receiving the combination of TCDD-treatment and T. gondii infection when compared to vehicle controls. The splenic cellularity as well as the percentage and absolute numbers of the CD4+ and CD8+ T cell subsets and the non-T cells were not altered in all the groups tested. The natural history of T. gondii infection was not altered following TCDD treatment as demonstrated by no significant differences in brain lesion scores and the number of tissue cysts in the brains of these mice.

scholarly journals Clinical Observation of the Number of Lymphocytes and T Cell Subsets in Patients with COVID-19 at Different Stages

2020 ◽  
Author(s):  
Jing Bai ◽  
Hui Zhou ◽  
Bao-sheng Dai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
White Blood Cells ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Subsets ◽  
Control Group ◽  
Cd8 Cells ◽  
Significant Difference ◽  
Severe Group

Abstract To explore the changes of lymphocytes and T cell subsets at different stages in patients with COVID-19. 86 patients with COVID-19 were enrolled, and the dynamic changes of peripheral blood lymphocytes and T cell subsets of CD3+, CD4+, and CD8+ were measured on admission, after treatment for1 week, 2 weeks, and before discharge. There were no significant differences in the number of white blood cells and lymphocytes between admission and 2 weeks after treatment or before discharge in severe patients. The counts of CD3+, CD4+, and CD8+ T cells decreased significantly on admission. After 2 weeks of treatment, the CD3+ counts were significantly higher than that on admission. The CD4+ and CD8+ counts increased significantly after 1 week of treatment, and went up remarkably before discharge compared with that on admission. There was no significant difference in the number of CD3+ cells between the mild group and the control group on admission, but it was significantly lower in the severe group than that in the control group and the mild group. The CD4+ and CD8+ counts decreased significantly in both mild and severe patients on admission, and increased significantly before discharge. At the time of discharge, the CD4+ counts in the severe and mild groups were still significantly lower than in the control group, but there was no significant difference in CD8+ counts among the three groups. The counts of CD3+,CD4+,and CD8+ T cells in the patients with COVID-19 is significantly correlated with the short-term prognosis, and is more sensitive than lymphocytes. In the earliest stage, the numbers of CD4+ and CD8+ cells are more sensitive to early reduction and faster to late recovery.

scholarly journals CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer

2020 ◽  
Author(s):  
Yasmin Vahidi ◽  
Mandana Bagheri ◽  
Abbas Ghaderi ◽  
Zahra Faghih
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Axillary Lymph ◽  
Memory Cells ◽  
Color Flow ◽  
Draining Lymph Nodes

Abstract Background: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8 + memory T cell subsets including stem memory T cells (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC). Methods: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8 + lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software. Results: We observed that 47.65±2.66% of CD8+ lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P=0.024 and P=0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO hi and CD45RO low subsets, and TSCM was higher in patients with stage II compared to those in stage I (P<0.05). In addition, the percentage of naive CD8 + T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P=0.025). Conclusions: Our data collectively indicate no significant differences in the frequencies of CD8 + lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 low TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45 low TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells’ differentiation (CD45RO low ), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.

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