scholarly journals Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7Rαhigh cell population in solid organ transplant recipients

2007 ◽  
Vol 204 (7) ◽  
pp. 1533-1541 ◽  
Author(s):  
Laura Codarri ◽  
Laure Vallotton ◽  
Donatella Ciuffreda ◽  
Jean-Pierre Venetz ◽  
Miguel Garcia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Chronic Rejection ◽  
Healthy Subjects ◽  
Cd4 T Cell ◽  
Transplant Proc ◽  
Cell Populations ◽  
Transplant Recipients

It has been recently shown (Seddiki, N., B. Santner-Nanan, J. Martinson, J. Zaunders, S. Sasson, A. Landay, M. Solomon, W. Selby, S.I. Alexander, R. Nanan, et al. 2006. J. Exp. Med. 203:1693–1700.) that the expression of interleukin (IL) 7 receptor (R) α discriminates between two distinct CD4 T cell populations, both characterized by the expression of CD25, i.e. CD4 regulatory T (T reg) cells and activated CD4 T cells. T reg cells express low levels of IL-7Rα, whereas activated CD4 T cells are characterized by the expression of IL-7Rαhigh. We have investigated the distribution of these two CD4 T cell populations in 36 subjects after liver and kidney transplantation and in 45 healthy subjects. According to a previous study (Demirkiran, A., A. Kok, J. Kwekkeboom, H.J. Metselaar, H.W. Tilanus, and L.J. van der Laan. 2005. Transplant. Proc. 37:1194–1196.), we observed that the T reg CD25+CD45RO+IL-7Rαlow cell population was reduced in transplant recipients (P < 0.00001). Interestingly, the CD4+CD25+CD45RO+IL-7Rαhigh cell population was significantly increased in stable transplant recipients compared with healthy subjects (P < 0.00001), and the expansion of this cell population was even greater in patients with documented humoral chronic rejection compared with stable transplant recipients (P < 0.0001). The expanded CD4+CD25+CD45RO+IL-7Rαhigh cell population contained allospecific CD4 T cells and secreted effector cytokines such as tumor necrosis factor α and interferon γ, thus potentially contributing to the mechanisms of chronic rejection. More importantly, CD4+IL-7Rα+and CD25+IL-7Rα+ cells were part of the T cell population infiltrating the allograft of patients with a documented diagnosis of chronic humoral rejection. These results indicate that the CD4+CD25+IL-7Rα+ cell population may represent a valuable, sensitive, and specific marker to monitor allospecific CD4 T cell responses both in blood and in tissues after organ transplantation.

scholarly journals CD32+and PD-1+Lymph Node CD4 T Cells Support Persistent HIV-1 Transcription in Treated Aviremic Individuals

2018 ◽  
Vol 92 (20) ◽  
Author(s):  
Alessandra Noto ◽  
Francesco A. Procopio ◽  
Riddhima Banga ◽  
Madeleine Suffiotti ◽  
Jean-Marc Corpataux ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Populations ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTA recent study conducted in blood has proposed CD32 as the marker identifying the “elusive” HIV reservoir. We have investigated the distribution of CD32+CD4 T cells in blood and lymph nodes (LNs) of HIV-1-uninfected subjects and viremic untreated and long-term-treated HIV-1-infected individuals and their relationship with PD-1+CD4 T cells. The frequency of CD32+CD4 T cells was increased in viremic compared to treated individuals in LNs, and a large proportion (up to 50%) of CD32+cells coexpressed PD-1 and were enriched within T follicular helper (Tfh) cells. We next investigated the role of LN CD32+CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32+and PD-1+CD4 T cells compared to CD32−and PD-1−cells in both viremic and treated individuals, but there was no difference between CD32+and PD-1+cells. There was no enrichment of latently infected cells with inducible HIV-1 in CD32+versus PD-1+cells in antiretroviral therapy (ART)-treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32+PD-1+CD4 T cells were significantly enriched in cell-associated HIV RNA compared to CD32−PD-1−(averages of 5.2-fold in treated individuals and 86.6-fold in viremics), CD32+PD-1−(2.2-fold in treated individuals and 4.3-fold in viremics), and CD32−PD-1+(2.2-fold in ART-treated individuals and 4.6-fold in viremics) cell populations. Similar levels of HIV-1 transcription were found in CD32+PD-1−and CD32−PD-1+CD4 T cells. Interestingly, the proportion of CD32+and PD-1+CD4 T cells negatively correlated with CD4 T cell counts and length of therapy. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and coexpression of CD32 and PD-1, the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals.IMPORTANCEThe existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication-competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells coexpressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription.

scholarly journals CD32+and PD-1+Lymph Node CD4 T Cells Support Persistent HIV-1 Transcription in Treated Aviremic Individuals

2018 ◽  
Author(s):  
Alessandra Noto ◽  
Francesco A. Procopio ◽  
Riddhima Banga ◽  
Madeleine Suffiotti ◽  
Jean-Marc Corpataux ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Populations ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTA recent study conducted in blood has proposed CD32 as the marker identifying the ‘elusive’ HIV reservoir. We have investigated the distribution of CD32+CD4 T cells in blood and lymph nodes(LNs) of healthy HIV-1 uninfected, viremic untreated and long-term treated HIV-1 infected individuals and their relationship with PD-1+CD4 T cells. The frequency of CD32+CD4 T cells was increased in viremic as compared to treated individuals in LNs and a large proportion(up to 50%) of CD32+cells co-expressed PD-1 and were enriched within T follicular helper cells(Tfh) cells. We next investigated the role of LN CD32+CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32+and PD-1+CD4 T cells as compared to CD32-and PD-1-cells in both viremic and treated individuals but there was no difference between CD32+and PD-1+cells. There was not enrichment of latently infected cells with inducible HIV-1 in CD32+versus PD-1+cells in ART treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32+PD-1+CD4 T cells were significantly enriched in cell associated HIV RNA as compared to CD32-PD-1-(average 5.2 fold in treated and 86.6 fold in viremics), to CD32+PD-1-(2.2 fold in treated and 4.3 fold in viremics) and to CD32-PD-1+cell populations(2.2 fold in ART treated and 4.6 fold in viremics). Similar levels of HIV-1 transcription were found in CD32+PD-1-and CD32-PD-1+CD4 T cells. Interestingly, the proportion of CD32+and PD-1+CD4 T cells negatively correlated with CD4 T cell counts and length of therapy while positively correlated with viremia. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and CD32 and PD-1 co-expression the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals.ImportanceThe existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells co-expressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription.

scholarly journals Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production

2012 ◽  
Vol 210 (1) ◽  
pp. 143-156 ◽  
Author(s):  
Matthieu Perreau ◽  
Anne-Laure Savoye ◽  
Elisa De Crignis ◽  
Jean-Marc Corpataux ◽  
Rafael Cubas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Productive Infection ◽  
Cell Populations ◽  
Cell Compartment ◽  
Tfh Cells ◽  
Follicular Helper

In the present study, we have investigated the distribution of HIV-specific and HIV-infected CD4 T cells within different populations of memory CD4 T cells isolated from lymph nodes of viremic HIV-infected subjects. Four memory CD4 T cell populations were identified on the basis of the expression of CXCR5, PD-1, and Bcl-6: CXCR5−PD-1−Bcl-6−, CXCR5+PD-1−Bcl-6−, CXCR5−PD-1+Bcl-6−, and CXCR5+PD-1+Bcl-6+. On the basis of Bcl-6 expression and functional properties (IL-21 production and B cell help), the CXCR5+PD-1+Bcl-6+ cell population was considered to correspond to the T follicular helper (Tfh) cell population. We show that Tfh and CXCR5−PD-1+ cell populations are enriched in HIV-specific CD4 T cells, and these populations are significantly increased in viremic HIV-infected subjects as compared with healthy subjects. The Tfh cell population contained the highest percentage of CD4 T cells harboring HIV DNA and was the most efficient in supporting productive infection in vitro. Replication competent HIV was also readily isolated from Tfh cells in subjects with nonprogressive infection and low viremia (<1,000 HIV RNA copies). However, only the percentage of Tfh cells correlated with the levels of plasma viremia. These results demonstrate that Tfh cells serve as the major CD4 T cell compartment for HIV infection, replication, and production.

Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3121-3127 ◽  
Author(s):  
Ester M. M. van Leeuwen ◽  
Ester B. M. Remmerswaal ◽  
Mirjam H. M. Heemskerk ◽  
Ineke J. M. ten Berge ◽  
Rene A. W. van Lier
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Target Cells ◽  
Dependent Manner ◽  
T Cell Clones ◽  
Strong Selection ◽  
Cell Clones

Abstract To obtain insight into human CD4+ T cell differentiation and selection in vivo, we longitudinally studied cytomegalovirus (CMV)–specific CD4+ T cells after primary infection. Early in infection, CMV-specific CD4+ T cells have the appearance of interferon γ (IFNγ)–producing T-helper 1 (TH1) type cells, whereas during latency a large population of CMV-specific CD4+CD28– T cells emerges with immediate cytotoxic capacity. We demonstrate that CD4+CD28– T cells could lyse CMV antigen–expressing target cells in a class II–dependent manner. To clarify the clonal relationship between early and late CMV-specific CD4+ T cells, we determined their Vβ usage and CDR3 sequences. The T-cell receptor β (TCRβ) diversity in the early CMV-specific CD4+ T-cell population was high in contrast to the use of a very restricted set of TCRβ sequences in latent infection. T-cell clones found in the late CMV-specific CD4+ T-cell population could not be retrieved from the early CD4+ T-cell population, or were present only at a low frequency. The observation that dominant CMV-specific CD4+ clones during latency were only poorly represented in the acute phase suggests that after the initial control of the virus strong selection and/or priming of novel clones takes place in persistent infections in humans.

scholarly journals Interferon γ Eliminates Responding Cd4 T Cells during Mycobacterial Infection by Inducing Apoptosis of Activated Cd4 T Cells

2000 ◽  
Vol 192 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Dyana K. Dalton ◽  
Laura Haynes ◽  
Cong-Qiu Chu ◽  
Susan L. Swain ◽  
Susan Wittmer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
Wild Type ◽  
Normal Numbers ◽  
Large Expansion ◽  
Ifn Γ

In Mycobacterium bovis Bacille Calmette-Guérin (BCG)-infected wild-type mice, there was a large expansion of an activated (CD44hi) splenic CD4 T cell population followed by a rapid contraction of this population to normal numbers. Contraction of the activated CD4 T cell population in wild-type mice was associated with increased apoptosis of activated CD4 T cells. In BCG-infected interferon (IFN)-γ knockout (KO) mice, the activated CD4 T cell population did not undergo apoptosis. These mice accumulated large numbers of CD4+CD44hi T cells that were responsive to mycobacterial antigens. Addition of IFN-γ to cultured splenocytes from BCG-infected IFN-γ KO mice induced apoptosis of activated CD4 T cells. IFN-γ–mediated apoptosis was abolished by depleting adherent cells or Mac-1+ spleen cells or by inhibiting nitric oxide synthase. Thus, IFN-γ is essential to a regulatory mechanism that eliminates activated CD4 T cells and maintains CD4 T cell homeostasis during an immune response.

scholarly journals Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.

1992 ◽  
Vol 175 (2) ◽  
pp. 331-340 ◽  
Author(s):  
H Groux ◽  
G Torpier ◽  
D Monté ◽  
Y Mouton ◽  
A Capron ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Death Process ◽  
Immunodeficiency Virus ◽  
Asymptomatic Individuals

In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.

The Comparison of the Cytobiological Role of Bone Marrow CD4+ T Cells in Aplastic Anemia Patients and Healthy Subjects.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3758-3758
Author(s):  
Miao Zheng ◽  
Wenli Liu ◽  
Jianfeng Zhou ◽  
Hanying Sun ◽  
Yicheng Zhang
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Healthy Subjects ◽  
Culture Supernatant ◽  
Normal Group ◽  
Cd4 T Cell ◽  
Cell Culture Supernatant ◽  
Cord Blood Cd34

Abstract Recent studies indicate that immune-associated aplastic anemia (AA) resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases. Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from AA patients peripheral blood and bone marrow (BM). In the current study, BM CD4+T cells were isolated from both AA patients and healthy subjects with immunomagnetic beads sorting and were compared with regard to proliferation capability, apoptosis features and the impacts of their secreted cytokines on hematopoiesis stem/progenitor cells. With the improved MTT method, BM CD4+T cells of AA group presented 1.6 times more enhanced reproductive activity than those of normal group. Induced by high concentrational CD3 monoclonal antibody for 18h, evident apoptosis cells could be seen under the electron microscope in both normal group and AA group. Quantified by flow cytometry using Annexin-V FITC/PI dual staining method, apoptosis rates in the early and advanced stages of AA group were more than those of normal group (P<0.01). Apoptosis rate in early stage: normal group(7.03±0.86)%, AA group(16.11±1.37)%; apoptosis rate in advanced stage: normal group(2.07±0.42)%, AA group(8.05±0.36)%. The influence of BM CD4+T cell culture supernatant on CFU-GM formation of cord blood CD34+ hematopoiesis stem/progenitor cells: the CFU-GM count in AA group was: (74.50±9.50)/104 cells; the CFU-GM count in normal group was: (124.25±19.80)/104 cells, observing under an inverted microscope. A significant difference was present in the comparison between the two groups (P<0.01). CyclinD3 mRNA and protein expression levels of cord blood CD34+ cells were both down-regulated induced by BM CD4+ T cell culture supernatant of AA patients. These results indicate a strong likelihood of an abnormally proliferative and activated state of BM CD4+T cells among AA patients and its intimate correlation with AA hematopoiesis failure by secreting some soluble humoral agents that are able to inhibit CyclinD3 and consequently suppress hematopoietic stem cell in proliferation.

scholarly journals Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1426
Author(s):  
Kerri Lal ◽  
Yuwadee Phuang-Ngern ◽  
Suchada Suhkumvittaya ◽  
Edwin Leeansyah ◽  
Aljawharah Alrubayyi ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Cell Population ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Acute Hiv ◽  
Hiv 1

CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.

Characterization of CD4+ T Cell Response Induced by p210-Derived Peptide Vaccinations in CML Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1808-1808
Author(s):  
Monica Bocchia ◽  
Micaela Ippoliti ◽  
Elisabetta Abruzzese ◽  
Maristella Tassi ◽  
Marzia Defina ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cell Response ◽  
Cd4 T Cells ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cd4 Cells ◽  
Thymidine Incorporation Assay ◽  
Incorporation Assay

Abstract We have previously shown that vaccination of chronic myelogenous leukaemia (CML) patients with CMLVAX100 (a mixture of 5 p210-b3a2 breakpoint derived peptides) plus GM-CSF was able to induce an evident and durable peptide-specific CD4+ T cell response in the majority of patients. Peptide-specific CD4+ T cell proliferation was measured by standard [3H] thymidine incorporation assay and this response was mainly mediated by a 25 mer long breakpoint peptide (b3a2-25) included in the vaccine. In this pilot clinical trial we showed that about 60% of 28 CML patients vaccinated while on imatinib, showed a reduction of their long lasting molecular residual disease after immunization (first 6 vaccinations) and about 25% of them achieved in addition a complete molecular response. To investigate the contribute of this peptide specific CD4+ T cell response in antitumor activity, we further characterize peptide-induced proliferating CD4+ cells. Briefly, in 10 CMLVAX100 vaccinated patients in which a strong b3a2-25 specific CD4+ proliferation was previously observed, we freshly isolated peripheral blood CD4+ T cells and we cultured them 4 days only in the presence or not of b3a2-25 vaccine peptide or control PR-25 peptide. Afterwards, each culture condition was analyzed both for the co-expression of CD25, perforin and FOXP3 molecules and for standard [3H] thymidine incorporation assay. As expected all patients showed a strong b3a2-25 specific CD4+ proliferation (mean stimulation index 43 -range 19–81-). When flow cytometric analysis was performed, we observed a consistent increase of two main CD4+ T cells subsets only in the b3a2-25 stimulated CD4+ T cells, not in “no peptide” or “control peptide” stimulated CD4+ T cells. a “small-size” CD4+/perforin+ T cell population (raising from a median of 1.06% (range 0.21–5.2) to 2.32% (range 0.49–6.2) with very likely cytotoxic activity a “large-size” CD4+/CD25+/FOXP3+ T cell population (raising from 0.29% (range 0.03–0.66) to 5.65% (range 0.71–9.5) with potential regulatory function. Since the large size of these cells and their high proliferative activity would argue against a regulatory features and considering that the immunophenotypic profile of Tregs in human is not yet fully defined we performed a functional test to measure a potential regulatory activity of these vaccine-induced T cell population. Thus, we evaluated the ability of b3a2-25 specific CD4+ T cells to inhibit the growth of CFSE labelled normal subjects naïve CD4+ T cells stimulated with autologous CD3-depleted APCs and antiCD3 MoAb. In our experimental conditions, naïve CFSE CD4+ T cells equally proliferated in the presence of b3a2-25 specific CD4+ cells, “no peptide” CD4+ cells or PR-25 control peptide CD4+ cells from vaccinated patients and the rate of proliferation was similar to the one observed in co-culture. experiments with allogeneic normal CD4+ cells. Our data suggest that the immune response induced in CML patients by CMLVAX100 vaccinations, consists of an increase of peptide-specific cytotoxic CD4+ T cells and a much more evident augment of CD4+/CD25+/FOXP3+ T cells that despite resembling a Treg phenotype display apparently no suppressive activity. The exact role of this peptide-specific CD4+ T cells subset in the context of CMLVAX100 mediated immune response needs to be further elucidated.

scholarly journals Reduced immune-regulatory molecule expression on human colonic memory CD4 T cells in older adults

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Stephanie M. Dillon ◽  
Tezha A. Thompson ◽  
Allison J. Christians ◽  
Martin D. McCarter ◽  
Cara C. Wilson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Older Persons ◽  
Age Groups ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cell Immunity ◽  
Memory Cd4 T Cells

Abstract Background The etiology of the low-level chronic inflammatory state associated with aging is likely multifactorial, but a number of animal and human studies have implicated a functional decline of the gastrointestinal immune system as a potential driver. Gut tissue-resident memory T cells play critical roles in mediating protective immunity and in maintaining gut homeostasis, yet few studies have investigated the effect of aging on human gut T cell immunity. To determine if aging impacted CD4 T cell immunity in the human large intestine, we utilized multi-color flow cytometry to measure colonic lamina propria (LP) CD4 T cell frequencies and immune-modulatory marker expression in younger (mean ± SEM: 38 ± 1.5 yrs) and older (77 ± 1.6 yrs) adults. To determine cellular specificity, we evaluated colon LP CD8 T cell frequency and phenotype in the same donors. To probe tissue specificity, we evaluated the same panel of markers in peripheral blood (PB) CD4 T cells in a separate cohort of similarly aged persons. Results Frequencies of colonic CD4 T cells as a fraction of total LP mononuclear cells were higher in older persons whereas absolute numbers of colonic LP CD4 T cells per gram of tissue were similar in both age groups. LP CD4 T cells from older versus younger persons exhibited reduced CTLA-4, PD-1 and Ki67 expression. Levels of Bcl-2, CD57, CD25 and percentages of activated CD38+HLA-DR+ CD4 T cells were similar in both age groups. In memory PB CD4 T cells, older age was only associated with increased CD57 expression. Significant age effects for LP CD8 T cells were only observed for CTLA-4 expression, with lower levels of expression observed on cells from older adults. Conclusions Greater age was associated with reduced expression of the co-inhibitory receptors CTLA-4 and PD-1 on LP CD4 T cells. Colonic LP CD8 T cells from older persons also displayed reduced CTLA-4 expression. These age-associated profiles were not observed in older PB memory CD4 T cells. The decline in co-inhibitory receptor expression on colonic LP T cells may contribute to local and systemic inflammation via a reduced ability to limit ongoing T cell responses to enteric microbial challenge.

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