scholarly journals Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

2015 ◽  
Vol 22 (5) ◽  
pp. 561-569 ◽  
Author(s):  
Lia de Rond ◽  
Rose-Minke Schure ◽  
Kemal Öztürk ◽  
Guy Berbers ◽  
Elisabeth Sanders ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Booster Vaccination ◽  
T Cell Memory ◽  
Effector Memory ◽  
Memory Cells ◽  
Cell Memory ◽  
Cell Responses ◽  
Specific Effector ◽  
Effector Memory Cells

ABSTRACTWhooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4+and CD8+T-cell fractions (CFSEdim) were higher in aP- than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4+effector memory cells (CD45RA−CCR7−) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP- and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4+and CD8+effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

scholarly journals Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates

2008 ◽  
Vol 118 (1) ◽  
pp. 294-305 ◽  
Author(s):  
Carolina Berger ◽  
Michael C. Jensen ◽  
Peter M. Lansdorp ◽  
Mike Gough ◽  
Carole Elliott ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Adoptive Transfer ◽  
Central Memory ◽  
T Cell Memory ◽  
Memory Cells ◽  
Cell Memory ◽  
Central Memory Cells

scholarly journals Convergent epitope-specific T cell responses after SARS-CoV-2 infection and vaccination

2021 ◽  
Author(s):  
Anastasia A Minervina ◽  
Mikhail V Pogorelyy ◽  
Allison M Kirk ◽  
Emma Kaitlynn Allen ◽  
Kim J Allison ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
T Cell Responses ◽  
T Cell Response ◽  
Critical Parameters ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cell Responses ◽  
Depth Analysis

SARS-CoV-2 mRNA vaccines, including Pfizer/Biontech BNT162b2, were shown to be effective for COVID-19 prevention, eliciting both robust antibody responses in naive individuals and boosting pre-existing antibody levels in SARS-CoV-2-recovered individuals. However, the magnitude, repertoire, and phenotype of epitope-specific T cell responses to this vaccine, and the effect of vaccination on pre-existing T cell memory in SARS-CoV-2 convalescent patients, are still poorly understood. Thus, in this study we compared epitope-specific T cells elicited after natural SARS-CoV-2 infection, and vaccination of both naive and recovered individuals. We collected peripheral blood mononuclear cells before and after BNT162b2 vaccination and used pools of 18 DNA-barcoded MHC-class I multimers, combined with scRNAseq and scTCRseq, to characterize T cell responses to several immunodominant epitopes, including a spike-derived epitope cross-reactive to common cold coronaviruses. Comparing responses after infection or vaccination, we found that T cells responding to spike-derived epitopes show similar magnitudes of response, memory phenotypes, TCR repertoire diversity, and αβTCR sequence motifs, demonstrating the potency of this vaccination platform. Importantly, in COVID-19-recovered individuals receiving the vaccine, pre-existing spike-specific memory cells showed both clonal expansion and a phenotypic shift towards more differentiated CCR7-CD45RA+ effector cells. In-depth analysis of T cell receptor repertoires demonstrates that both vaccination and infection elicit largely identical repertoires as measured by dominant TCR motifs and receptor breadth, indicating that BNT162b2 vaccination largely recapitulates T cell generation by infection for all critical parameters. Thus, BNT162b2 vaccination elicits potent spike-specific T cell responses in naive individuals and also triggers the recall T cell response in previously infected individuals, further boosting spike-specific responses but altering their differentiation state. Overall, our study demonstrates the potential of mRNA vaccines to induce, maintain, and shape T cell memory through vaccination and revaccination.

scholarly journals Memories that last forever: strategies for optimizing vaccine T-cell memory

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1678-1689 ◽  
Author(s):  
Jeffrey D. Ahlers ◽  
Igor M. Belyakov
Keyword(s):  
T Cell ◽  
Central Memory ◽  
T Cell Memory ◽  
Effector Memory ◽  
Cell Vaccine ◽  
High Avidity ◽  
Memory Cells ◽  
Cell Memory ◽  
Mucosal Transmission ◽  
Mucosal Surfaces

Abstract For acute self-limiting infections a vaccine is successful if it elicits memory at least as good as the natural experience; however, for persistent and chronic infections such as HIV, hepatitis C virus (HCV), human papillomavirus (HPV), and human herpes viruses, this paradigm is not applicable. At best, during persistent virus infection the person must be able to maintain the integrity of the immune system in equilibrium with controlling replicating virus. New vaccine strategies are required that elicit both potent high-avidity CD8+ T-cell effector/memory and central memory responses that can clear the nidus of initial virus-infected cells at mucosal surfaces to prevent mucosal transmission or significantly curtail development of disease. The objective of an HIV-1 T-cell vaccine is to generate functional CD8+ effector memory cells at mucosal portals of virus entry to prevent viral transmission. In addition, long-lived CD8+ and CD4+ central memory cells circulating through secondary lymphoid organs and resident in bone marrow, respectively, are needed to provide a concerted second wave of defense that can contain virus at mucosal surfaces and prevent systemic dissemination. Further understanding of factors which can influence long-lived effector and central memory cell differentiation will significantly contribute to development of effective T-cell vaccines. In this review we will focus on discussing mechanisms involved in T-cell memory and provide promising new approaches toward expanding current vaccine strategies to enhance antiviral memory.

scholarly journals Expansion of Stem Cell-Like CD4+Memory T Cells during Acute HIV-1 Infection Is Linked to Rapid Disease Progression

2019 ◽  
Vol 93 (14) ◽  
Author(s):  
Jernej Pušnik ◽  
Michael A. Eller ◽  
Boonrat Tassaneetrithep ◽  
Bruce T. Schultz ◽  
Leigh Anne Eller ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Disease Progression ◽  
Cell Subset ◽  
T Cell Memory ◽  
Effector Memory ◽  
Cell Memory ◽  
Acute Hiv ◽  
Hiv 1

ABSTRACTAcute HIV-1 infection is characterized by high viremia and massive depletion of CD4+T cells throughout all tissue compartments. During this time the latent viral reservoir is established but the dynamics of memory CD4+T cell subset development, their infectability and influence on disease progression during acute HIV-1 infection has not been carefully described. We therefore investigated the dynamics of CD4+T cell memory populations in the RV217 (ECHO) cohort during the acute phase of infection. Interestingly, while we found only small changes in central or effector memory compartments, we observed a profound expansion of stem cell-like memory CD4+T cells (SCM) (2.7-fold;P < 0.0001). Furthermore, we demonstrated that the HIV-1 integration and replication preferentially take place in highly differentiated CD4+T cells such as transitional memory (TM) and effector memory (EM) CD4+T cells, while naive and less mature memory cells prove to be more resistant. Despite the relatively low frequency of productively infected SCM, we suggest that their quiescent phenotype, increased susceptibility to HIV-1 integration compared to naive cells and extensive expansion make them one of the key players in establishment and persistence of the HIV-1 reservoir. Moreover, the expansion of SCM in acute HIV-1 infection was a result of Fas upregulation on the surface of naive CD4+T cells. Interestingly, the upregulation of Fas receptor and expansion of SCM in acute HIV-1 infection was associated with the early viral set point and disease progression (rho = 0.47,P = 0.02, and rho = 0.42,P = 0.041, respectively). Taken together, our data demonstrate an expansion of SCM during early acute HIV-1 infection which is associated with disease outcome.IMPORTANCEUnderstanding the immunopathology of acute HIV-1 infection will help to develop eradication strategies. We demonstrate here that a CD4+T cell memory subset expands during acute HIV-1 infection, which is associated with disease progression.

scholarly journals T cell memory is short-lived in the absence of antigen.

1991 ◽  
Vol 174 (5) ◽  
pp. 969-974 ◽  
Author(s):  
D Gray ◽  
P Matzinger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Immunological Memory ◽  
Traditional View ◽  
T Cell Memory ◽  
Memory Cells ◽  
Cell Memory ◽  
Independent State ◽  
Dependent Process

Immunological memory has generally been ascribed to the development of long-lived memory cells that can persist for years in the absence of renewed antigenic encounter. In the experiments reported here, we have adoptively transferred memory T cells in the presence and absence of priming antigen and assessed their functional survival. The results indicate that, in contrast to the traditional view, the maintenance of T cell memory requires the presence of antigen, suggesting that memory, like tolerance, is an antigen-dependent process rather than an antigen-independent state.

Chemotherapy-Resistant T Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-51-SCI-51
Author(s):  
Cameron J. Turtle
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Cytotoxic Chemotherapy ◽  
T Cell Memory ◽  
Effector Memory ◽  
Tcr Signaling ◽  
Cell Memory ◽  
Cd8 Cells

Abstract Abstract SCI-51 The mechanisms that maintain human T cell memory during normal and perturbed homeostasis are not fully understood. Patients undergoing multiple cycles of cytotoxic chemotherapy infrequently develop infections with viruses that are controlled by memory CD8+ T cells either during or after the period of profound lymphocytopenia, suggesting that some memory cells survive chemotherapy and provide protective immunity. We recently identified a subset of quiescent human CD161hi CD8+ T cells characterized by the capacity to rapidly efflux cytotoxic drugs and the fluorescent dye, rhodamine 123 (Rh123), which endowed them with the ability to survive chemotherapy in vitro and in vivo and to contribute to the recovery of lymphocyte numbers in patients receiving chemotherapy. Rh123 effluxing CD161hi memory CD8+ cells were identified in both the CD62L+ central memory (CM) and CD62L- effector memory (EM) pools, and were characterized by uniform expression of CD28, high levels of bcl-2, and low levels of granzyme B and perforin. CD161 and CD62L expression allowed partitioning of the CD8+ memory compartment into four phenotypic subsets with distinct transcriptional profiles and functional properties. Gene expression profiling of Rh123 effluxing CD161hi memory CD8+ cells in both CM and EM pools revealed a type 17 differentiation program with high levels of RORC, RORA, IL23R, CCR6, KLRB1, and CCL20, compared with CD161lo CM and EM cells. Transcriptional profiling also revealed alterations in the T cell receptor (TCR) signaling pathway in CD161hi cells that limits their capacity to proliferate and secrete cytokines, including IL-17, after TCR stimulation. Despite stringent regulation of TCR signaling in type 17-programmed CD161hi cells, proliferation and cytokine secretion could be induced by ligating CD28 to provide costimulation, and by IL-1β, IL-12, IL-18 or IL-23. The nature of the second and third signals provided to CD161hi T cells revealed plasticity in this subset of cells and determined whether the CD161hi progeny derived after expansion had the capacity to secrete IL-17, or had differentiated to Tc1-like cells with restored capacity to proliferate to TCR ligation alone. Thus, a surprisingly large fraction of the human CD8+ T cell memory pool is comprised of CD161hi CD8+ T cells that express a type 17 transcriptional program and possess drug efflux capacity that allows them to survive cytotoxic chemotherapy and contribute to recovery of lymphocyte numbers. The stringent regulation of CD8+CD161+ memory T cells in normal physiology also suggests that this subset may have a potential role in the pathogenesis of IL-17-mediated inflammatory diseases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CONTENTS OF CD4+ AND CD8+ EFFECTOR MEMORY CELLS AND PROLIFERATIVE ACTIVITY OF T LYMPHOCYTES IN BRONCHIAL ASTHMA

2019 ◽  
Vol 21 (3) ◽  
pp. 503-516
Author(s):  
M. Sh. Barkovskaya ◽  
E. A. Blinova ◽  
L. V. Grishina ◽  
M. I. Leonova ◽  
V. M. Nepomniashchikch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Bronchial Asthma ◽  
Proliferative Activity ◽  
Memory T Cells ◽  
Effector Memory ◽  
Memory Cells ◽  
Healthy Donors ◽  
Effector Memory Cells

Bronchial asthma is a chronic inflammatory disease of the respiratory tract. T-lymphocytes play a key role in pathogenesis of this allergic disease. The reduction in number of naïve T cells and the accumulation of memory T cells in bronchial asthma are accompanied by dysregulation of T lymphocyte function. In present study, we have investigated the contents of different T lymphocyte subpopulations in peripheral blood as well as in resting and PHA-stimulated cultures, along with their proliferative capacity in patients with bronchial asthma and healthy donors. The study included 10 patients with bronchial asthma (age 45.4±11.8 years). One-half of patients was in remission state, the others having been at the stage of clinical exacerbation. The group of donors was formed by healthy individuals matched by gender and age to the patients. Based on expression of cell surface markers CD45R0, CD62L and CD197 (CCR7), the CD4+ and CD8+T lymphocytes were divided into central (Tcm) and effector memory cells (Tem), naïve T lymphocytes (Tnaïve) and terminally differentiated effector cells (Temra) using flow cytometry technique. The proliferative activity of Tcm, Tem and Tnaïve was evaluated in response to PHA as a functional marker of T cells. We have found that the percentage of peripheral CD4+TemCD62L+ and CD8+TemCD62L+ cells in the patients with asthma exacerbation was significantly reduced, if compared to the donors. Following PHA stimulation, these differences in T cell subsets between the groups of patients and donors were not detectable. We performed a correlation analysis between the memory T cell contents and age of the subjects studied. It was shown that the relative amounts of CD4+ and CD8+ memory cells increased with age in asthmatics, but not in healthy donors. Analysis of mitogen-induced proliferation showed that Tcm and Tnaïve cells proliferated more actively than other subpopulations in both groups. Meanwhile, the proliferative activity of CD4+T lymphocytes and subsets of CD8+Tcm, CD4+Tcm and CD4+Tem62L was higher in the group of asthma patients in remission state than in the patients with exacerbating disease, and healthy donors. The revealed increase in the relative number of memory T cells with age suggests that these cells participate in development of bronchial asthma. Proliferative response of the studied subpopulations, which was comparable to the donor values, suggests a functional maintenance of memory T cells and naïve T lymphocytes in bronchial asthma. The increased proliferation of some T-cell subpopulations in asthmatics in remission suggests an activated state of memory T cells. The observed decrease in the number of CD4+TemCD62L+ and CD8+TemCD62L+ in patients with asthma exacerbation may be, by our opinion, associated with an active inflammatory process in the airways.

Lenalidomide (CC5013, Revlimid®) Alters a T Cell Homeostatic Check-Point in Patients with Myelodysplastic Syndrome (MDS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 851-851
Author(s):  
JianXiang Zou ◽  
Edna Ku ◽  
Fanqi Bai ◽  
Jeffrey S. Painter ◽  
Alan F. List ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Effector Memory ◽  
T Cell Proliferation ◽  
Memory Cells ◽  
Tcr Repertoire ◽  
Effector Memory Cells

Abstract Background: Myelodysplastic Syndromes (MDS) are a diverse group of myeloid malignancies that occur primarily in older individuals. Several distinct immunologic abnormalities have been described in MDS, including concurrent autoimmune diseases, inversion of CD4+ and CD8+ cell populations, and expansion hematopoietic inhibitory) CD8+ T cell clones. Suppression of hematopoiesis by T cells has been implicated in the pathogenesis of ineffective hematopoiesis in a select subpopulation of patients with response to immunosuppressive therapy. Immunologic abnormalities in MDS patients may relate to the process of immunologic aging associated with functional deterioration. Lenalidomide (CC5013, Revlimid®, Celgene Inc) is a member of a proprietary drug class known as immunomodulatory drugs (IMiDs) with strong and sustained hematological activity in MDS patients. The goal of this study was to investigate the in vitro and in vivo actions of lenalidomide on T cell immune functions and homeostasis in MDS patients. Methods: Using peripheral blood mononuclear cells (PBMCs), we analyzed T cell subpopulations and function in 11 MDS patients and 12 controls of similar age. Naïve and memory CD4 and CD8 T cell sub-populations were segregated by expression of CD45RA and CD62L expression by flow cytometry. After antigen activation with anti-CD3-cross-linking and allogeneic dendritic cells (allo-DCs), T cell proliferation was assessed by Brdu incorporation in CD4+ and CD8+ T cells, and intracellular cytokines determined by flow cytometry. T cell receptor (TCR) repertoire skewing was determined by CDR3-length analysis on 53 patients. In vivo action of lenalidomide was evaluated in PBMCs from seven patients (4 erythroid complete responders and 3 non-responders) taken pre- and post-treatment. Results: Patients with MDS had reduced T cell proliferation and impaired Th1 cytokine response after antigen stimulation compared to age-matched controls. No correlation was found between patient age and percentage of proliferating antigen-induced CD4− or CD8− T cells (r=0.13, p=0.6 and r=−0.17, p=0.5, respectively). Phenotype analysis showed that the percentage of CD4+ and CD8+/CD45RA+/CD62L+−naïve T cells were significantly reduced, whereas, CD4+ and CD8+/CD45RA−/CD62L−double-negative effector memory cells were significantly increased in MDS patients. Furthermore, 50% of MDS patients displayed a skewed T cell receptor repertoire that was not age-dependent. Of the MDS patients treated with lenalidomide, the four responders displayed a significant increase in antigen-induced T cell proliferation and increased Th1-type cytokine secretion, whereas no changes were observed in non-responders. Moreover, CD4+ (P=0.001) and CD8+ (P=0.06) T cells with a naïve phenotype increased accompanied by augmentation in the percentage of CD8+ central memory T cells (P=0.02); whereas, the percentage of CD4+ effector memory cells decreased (p=0.001) in lenalidomide responders but not in non-responders. Conclusions: These data suggest that MDS patients possess multiple T cell defects including age-independent TCR repertoire skewing, reduction in naïve T cells, and accumulation of effector memory cells that are improved by lenalidomide. Our findings suggest hematopoietic response to lenalidomide may relate to a novel capacity to restore T cell homeostasis.

Sign in / Sign up

Export Citation Format

Share Document