scholarly journals Sustained High Frequencies of Specific CD4 T Cells Restricted to a Single Persistent Virus

2002 ◽  
Vol 76 (8) ◽  
pp. 3748-3755 ◽  
Author(s):  
Martina Sester ◽  
Urban Sester ◽  
Barbara Gärtner ◽  
Boris Kubuschok ◽  
Matthias Girndt ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Acute Infection ◽  
T Cell Response ◽  
Proliferative Potential ◽  
Effector Cells ◽  
High Frequencies ◽  
Persistent Virus ◽  
High Level

ABSTRACT Replication of cytomegalovirus (CMV) is largely controlled by the cellular arm of the immune response. In this study the CMV-specific CD4 T-cell response was characterized in a cohort of apparently healthy individuals. In 11% of all individuals, extremely high frequencies, between 10 and 40%, were found. High-level frequencies of CMV-specific CD4 T cells persisted over several months and were not the result of an acute infection. Specific T cells were oligoclonal and were phenotypically and functionally characterized as mature effector cells, with both cytokine-secreting and proliferative potential. These high-level frequencies do not seem to compromise the immune response towards heterologous infections, and no signs of immunopathology were observed. Whereas a large temporary expansion of virus-specific T cells is well known to occur during acute infection, we now show that extremely high frequencies of virus-specific T cells may continuously exist in chronic CMV infection without overtly compromising the remaining protective immunity.

scholarly journals Race between Retroviral Spread and CD4+ T-Cell Response Determines the Outcome of Acute Friend Virus Infection

2009 ◽  
Vol 83 (21) ◽  
pp. 11211-11222 ◽  
Author(s):  
Rebecca Pike ◽  
Andrew Filby ◽  
Mickaël J.-Y. Ploquin ◽  
Urszula Eksmond ◽  
Rute Marques ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Acute Infection ◽  
T Cell Response ◽  
Friend Virus ◽  
Antiviral Immune Response ◽  
Ultimate Failure ◽  
Necessary And Sufficient

ABSTRACT Retroviruses can establish persistent infection despite induction of a multipartite antiviral immune response. Whether collective failure of all parts of the immune response or selective deficiency in one crucial part underlies the inability of the host to clear retroviral infections is currently uncertain. We examine here the contribution of virus-specific CD4+ T cells in resistance against Friend virus (FV) infection in the murine host. We show that the magnitude and duration of the FV-specific CD4+ T-cell response is directly proportional to resistance against acute FV infection and subsequent disease. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4+ T cells in the absence of a virus-specific CD8+ T-cell or B-cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility or coinfection with Lactate dehydrogenase-elevating virus (LDV) causes a proportional increase in the number of FV-specific CD4+ T cells required to control FV-induced disease. Furthermore, ultimate failure of FV/LDV coinfected hosts to control FV-induced disease is accompanied by accelerated contraction of the FV-specific CD4+ T-cell response. Conversely, an increased frequency or continuous supply of FV-specific CD4+ T cells is both necessary and sufficient to effectively contain acute infection and prevent disease, even in the presence of coinfection. Thus, these results suggest that FV-specific CD4+ T cells provide significant direct protection against acute FV infection, the extent of which critically depends on the ratio of FV-infected cells to FV-specific CD4+ T cells.

scholarly journals Mycobacterium tuberculosis Immune Response in Patients With Immune-Mediated Inflammatory Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Elisa Petruccioli ◽  
Linda Petrone ◽  
Teresa Chiacchio ◽  
Chiara Farroni ◽  
Gilda Cuzzi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Developed Countries ◽  
Preventive Therapy ◽  
T Cell Response ◽  
Specific Response ◽  
Immune Biomarkers ◽  
Immune Mediated

Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have an intrinsic higher probability to develop active-tuberculosis (TB) compared to the general population. The risk ranges from 2.0 to 8.9 in RA patients not receiving therapies. According to the WHO, the RA prevalence varies between 0.3% and 1% and is more common in women and in developed countries. Therefore, the identification and treatment of TB infection (TBI) in this fragile population is important to propose the TB preventive therapy. We aimed to study the M. tuberculosis (Mtb) specific T-cell response to find immune biomarkers of Mtb burden or Mtb clearance in patients with different TB status and different risk to develop active-TB disease. We enrolled TBI subjects as example of Mtb-containment, the active-TB as example of a replicating Mtb status, and the TBI-IMID as fragile population. To study the Mtb-specific response in a condition of possible Mtb sterilization, we longitudinally enrolled TBI subjects and active-TB patients before and after TB therapy. Peripheral blood mononuclear cells were stimulated overnight with Mtb peptides contained in TB1- and TB2-tubes of the Quantiferon-Plus kit. Then, we characterized by cytometry the Mtb-specific CD4 and CD8 T cells. In TBI-IMID, the TB therapy did not affect the ability of CD4 T cells to produce interferon-γ, tumor necrosis factor-α, and interleukin-2, their functional status, and their phenotype. The TB therapy determined a contraction of the triple functional CD4 T cells of the TBI subjects and active-TB patients. The CD45RA- CD27+ T cells stood out as a main subset of the Mtb-specific response in all groups. Before the TB-preventive therapy, the TBI subjects had higher proportion of Mtb-specific CD45RA-CD27+CD4+ T cells and the active-TB subjects had higher proportion of Mtb-specific CD45RA-CD27-CD4+ T cells compared to other groups. The TBI-IMID patients showed a phenotype similar to TBI, suggesting that the type of IMID and the IMID therapy did not affect the activation status of Mtb-specific CD4 T cells. Future studies on a larger and better-stratified TBI-IMID population will help to understand the change of the Mtb-specific immune response over time and to identify possible immune biomarkers of Mtb-containment or active replication.

Cellular side of acquired immunity (T cells)

2013 ◽  
Author(s):  
Assia Eljaafari ◽  
Pierre Miossec
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Disease Process ◽  
T Cell Response ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Immune Effector ◽  
Effector Cells ◽  
Th22 Cells

The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.

scholarly journals Regulation of T Cells in Cancer by Nitric Oxide

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2655
Author(s):  
Inesa Navasardyan ◽  
Benjamin Bonavida
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Target Cells ◽  
Effector Cells ◽  
Cell Functions

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.

Identification of New Alloantigen-Reactive CD8+ Cytotoxic and Suppressor T Cell Subpopulations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3229-3229
Author(s):  
Osnat Bohana-Kashtan ◽  
Hyam Levitsky ◽  
Curt I. Civin
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Suppressor T Cell ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

We sought to develop a better understanding of the T cells involved in the human allogeneic immune response, in order to eventually engineer a donor graft with reduced GVHD-mediating potential, without ablating general immune competence. Prior studies reported that all the activated CD4+ T cells responding to a specific antigen challenge reside within the CD4high population expressing high levels of membrane CD4. We identified a new population of activated CD8+ T cells that developed during an in vitro allogeneic immune response, along with the allo-activated CD4high T cell population. Analogous to activated CD4+ T cells, this new T cell population was distinguished by up-regulated CD8 (and CD38) expression (CD8highCD38+). In accordance with Martins et al. (Blood 2004, 104:3429), we found that the depletion of the CD4highCD38+ population resulted in reduced 2o response to the original 2nd party stimulators. In contrast, depletion of the CD8highCD38+ population resulted in an increased 2o response to 2nd party cells, with no change in the response to 3rd party or CMV antigens. Elevated numbers of CD8highCD38+ T cells potently reduced the 1o and 2o responses to 2nd party, but not to 3rd party cells or CMV antigens. The complementary, non-activated CD8normalCD38− T cell population had no inhibitory effect. Importantly, we found that CD8highCD38+ T cells mediated both a specific cytotoxic response (that could be inhibited by the pan-caspase inhibitor, Z-VAD), and a specific suppressive response toward the original 2nd party stimulators (that was not affected by Z-VAD), and within this CD8highCD38+ population, there was a subpopulation of cytotoxic T cells (perforin+LAMP1+CD56+CD11b+CD11c+) and a subpopulation of non-cytotoxic T cells. Furthermore, we found that although CD8highCD38+ T cells differentially expressed CD28, both CD8highCD38+CD28− and CD8highCD38+CD28− T cells mediated a cytotoxic as well as a suppressor T cell response toward the original 2nd party cells (different from the published suppressive function of CD8+CD28− T cells observed by Liu et al, Int Immunol 1998, 10:775). Upon separation of cytotoxic CD8highCD38+ T cells from suppressor CD8highCD38+ T cells, we will explore the GVHD potential of these 2 novel activated CD8high T cell subpopulations, in a sensitive in vivo xenograft model for GVHD using NOD/SCID/IL2Rγnull immunodeficient mice.

scholarly journals Functionally Heterogeneous CD8+ T-Cell Memory Is Induced by Sendai Virus Infection of Mice

1999 ◽  
Vol 73 (9) ◽  
pp. 7278-7286 ◽  
Author(s):  
Edward J. Usherwood ◽  
Robert J. Hogan ◽  
Graham Crowther ◽  
Sherri L. Surman ◽  
Twala L. Hogg ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Sendai Virus ◽  
T Cell Memory ◽  
Proliferative Potential ◽  
Proliferating Cells ◽  
Effector Cells ◽  
High Frequencies ◽  
Cd8 T Cell Memory

ABSTRACT It has recently been established that memory CD8+ T cells induced by viral infection are maintained at unexpectedly high frequencies in the spleen. While it has been established that these memory cells are phenotypically heterogeneous, relatively little is known about the functional status of these cells. Here we investigated the proliferative potential of CD8+ memory T cells induced by Sendai virus infection. High frequencies of CD8+ T cells specific for both dominant and subdominant Sendai virus epitopes persisted for many weeks after primary infection, and these cells were heterogeneous with respect to CD62L expression (approximately 20% CD62Lhi and 80% CD62Llo). Reactivation of these cells with the antigenic peptide in vitro induced strong proliferation of antigen-specific CD8+ T cells. However, approximately 20% of the cells failed to proliferate in vitro in response to a cognate peptide but nevertheless differentiated into effector cells and acquired full cytotoxic potential. These cells also expressed high levels of CD62L (in marked contrast to the CD62Llo status of the proliferating cells in the culture). Direct isolation of CD62Lhi and CD62LloCD8+ T cells from memory mice confirmed the correlation of this marker with proliferative potential. Taken together, these data demonstrate that Sendai virus infection induces high frequencies of memory CD8+ T cells that are highly heterogeneous in terms of both their phenotype and their proliferative potential.

High frequencies of Th1-type CD4+ T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1–associated myelopathy/tropical spastic paraparesis

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3335-3341 ◽  
Author(s):  
Peter K. C. Goon ◽  
Emmanuel Hanon ◽  
Tadahiko Igakura ◽  
Yuetsu Tanaka ◽  
Jonathan N. Weber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Inflammatory Diseases ◽  
Spastic Paraparesis ◽  
T Cell Response ◽  
Tropical Spastic Paraparesis ◽  
Cd4 T Cell ◽  
High Frequencies ◽  
T Lymphotropic Virus

Abstract CD4+ T cells are critical for inducing and maintaining efficient humoral and cellular immune responses to pathogens. The CD4+ T-cell response in human T-lymphotropic virus 1 (HTLV-1) infection has not been studied in detail. However, CD4+ T cells have been shown to predominate in early lesions in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). We present direct estimates of HTLV-1 Env- and Tax-specific CD4+ T-cell frequencies in patients infected with HTLV-1. We first showed that there was a strong bias toward the Th1 phenotype in these HTLV-1–specific CD4+ T cells in patients with HAM/TSP. We then demonstrated significantly higher frequencies of HTLV-1–specific Th1-type CD4+ T cells in HAM/TSP patients than in asymptomatic HTLV-1 carriers. The majority of these HTLV-1–specific CD4+ T cells did not express HTLV-1 Tax and were therefore unlikely to be infected by HTLV-1. High frequencies of activated HTLV-1–specific CD4+ T cells of the Th1 phenotype might contribute to the initiation or pathogenesis of HAM/TSP and other HTLV-1–associated inflammatory diseases.

scholarly journals Genome Wide DNA Methylation Landscape Reveals Glioblastoma Mediated Epigenetic Modification in Tumor Infiltrating CD4+ T-Cells

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Sreenivasulu Chintala ◽  
Kaleigh Fetcko ◽  
Mario Henriquez ◽  
Sheng Liu ◽  
Jun Wan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Gene Expression Profile ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Epigenetic Modification ◽  
Methylation Status ◽  
T Cell Response

Abstract INTRODUCTION CD4+ helper T (Th) cells initiate and maintain adaptive immune responses and play a critical role in orchestrating effective antitumor immune response. Although recent immunotherapeutic strategies have shown promising results against glioblastoma, the full potential of this modality has yet to be achieved. One of the major limitations of immunotherapy is the poor efficacy of antiglioblastoma T-cell response in the tumor microenvironment. We hypothesized that glioblastoma modulates antitumor T-cell response by epigenetic modification of tumor infiltrating Th cells (TIThC). METHODS To investigate the influence of glioblastoma on TIThCs, we isolated CD4+ T-cells from the tumor and peripheral blood (PB) of 5 steroid naïve patients with newly diagnosed glioblastoma and performed whole-genome bisulfite sequencing (WGBS) as well as RNAseq and identified differentially methylated and expressed genes between the two cell populations. RESULTS Our results show that glioblastoma mediated epigenetic modifications define the molecular characteristics of glioblastoma infiltrating CD4+ T-cells. Tegmentation based WGBS revealed more than 25 000 regions that are methylated differentially in pairwise comparison of TIThC and PB CD4+ T-cells. Methylation status correlated with the gene expression profile with more than 20 000 differentially expressed genes in TIThCs compared to PB. Of the CD4 lineage specific genes, TBX21, GATA3, RORC, and FOXP3, TBX21, GATA3, and FOXP3 showed differential methylation and expression level in TIThC; whereas, RORC only showed difference in methylation status but not in gene expression level. There was a significant difference in overall and CD4 lineage specific methylation and gene expression profile between patients. Pathway analysis of differentially methylated regions and differentially expressed genes indicated several pathways of tumor induced deregulation, including those involved in T-cell activation, lymphocyte differentiation, regulation of immune effector process, and cytokine production. CONCLUSION Glioblastoma multiforme (GBM) regulates antitumor immune response by significant epigenetic reprogramming of TIThC; thus, influencing their lineage specific differentiation and function.

scholarly journals An Optimized CD4 T-Cell Response Can Control Productive and Latent Gammaherpesvirus Infection

2004 ◽  
Vol 78 (13) ◽  
pp. 6827-6835 ◽  
Author(s):  
Rebecca L. Sparks-Thissen ◽  
Douglas C. Braaten ◽  
Scott Kreher ◽  
Samuel H. Speck ◽  
Herbert W. Virgin
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Acute Infection ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell

ABSTRACT CD4 T cells are important for control of infection with murine gammaherpesvirus 68 (γHV68), but it is not known whether CD4 T cells function via provision of help to other lymphocyte subsets, such as B cells and CD8 T cells, or have an independent antiviral function. Moreover, under conditions of natural infection, the CD4 T-cell response is not sufficient to eliminate infection. To determine the functional capacities of CD4 T cells under optimal or near-optimal conditions and to determine whether CD4 T cells can control γHV68 infection in the absence of CD8 T cells or B cells, we studied the effect of ovalbumin (OVA)-specific CD4 T cells on infection with a recombinant γHV68 that expresses OVA. OVA-specific CD4 T cells limited acute γHV68 replication and prolonged the life of infected T-cell receptor-transgenic RAG (DO.11.10/RAG) mice, demonstrating CD4 T-cell antiviral activity, independent of CD8 T cells and B cells. Despite CD4 T-cell-mediated control of acute infection, latent infection was established in DO.11.10/RAG mice. However, OVA-specific CD4 T cells reduced the frequency of latently infected cells both early (16 days postinfection) and late (42 days postinfection) after infection of mice containing CD8 T cells and B cells (DO.11.10 mice). These results show that OVA-specific CD4 T cells have B-cell and CD8 T-cell-independent antiviral functions in the control of acute infection and can, in the absence of preexisting CD8 T-cell or B-cell immunity, inhibit the establishment of gammaherpesvirus latency.

scholarly journals Legend of the Sentinels: Development of Lung Resident Memory T Cells and Their Roles in Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Youkun Qian ◽  
Yicheng Zhu ◽  
Yangyang Li ◽  
Bin Li
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Memory T Cells ◽  
Acute Infection ◽  
Effector T Cells ◽  
T Cell Response ◽  
The World ◽  
Pull Strategy ◽  
Resident Memory T Cells

SARS-CoV-2 is wreaking havoc around the world. To get the world back on track, hundreds of vaccines are under development. A deeper understanding of how the immune system responds to SARS-CoV-2 re-infection will certainly help. Studies have highlighted various aspects of T cell response in resolving acute infection and preventing re-infections. Lung resident memory T (TRM) cells are sentinels in the secondary immune response. They are mostly differentiated from effector T cells, construct specific niches and stay permanently in lung tissues. If the infection recurs, locally activated lung TRM cells can elicit rapid immune response against invading pathogens. In addition, they can significantly limit tumor growth or lead to pathologic immune responses. Vaccines targeting TRM cells are under development, with the hope to induce stable and highly reactive lung TRM cells through mucosal administration or “prime-and-pull” strategy. In this review, we will summarize recent advances in lung TRM cell generation and maintenance, explore their roles in different diseases and discuss how these cells may guide the development of future vaccines targeting infectious disease, cancer, and pathologic immune response.

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