scholarly journals Longitudinal Analysis of Dengue Virus–Specific Memory T Cell Responses and Their Association With Clinical Outcome in Subsequent DENV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Luis Alberto Sanchez-Vargas ◽  
Kathryn B. Anderson ◽  
Anon Srikiatkhachorn ◽  
Jeffrey R. Currier ◽  
Heather Friberg ◽  
...  
Keyword(s):  
T Cells ◽  
Clinical Outcome ◽  
Dengue Virus ◽  
Memory T Cells ◽  
Ex Vivo ◽  
Secondary Infection ◽  
Denv Infection ◽  
Memory T Cell ◽  
Cell Responses ◽  
Specific Memory

Memory T cells resulting from primary dengue virus (DENV) infection are hypothesized to influence the clinical outcome of subsequent DENV infection. However, the few studies involving prospectively collected blood samples have found weak and inconsistent associations with outcome and variable temporal trends in DENV-specific memory T cell responses between subjects. This study used both ex-vivo and cultured ELISPOT assays to further evaluate the associations between DENV serotype-cross-reactive memory T cells and severity of secondary infection. Using ex-vivo ELISPOT assays, frequencies of memory T cells secreting IFN-γ in response to DENV structural and non-structural peptide pools were low in PBMC from multiple time points prior to symptomatic secondary DENV infection and showed a variable response to infection. There were no differences in responses between subjects who were not hospitalized (NH, n=6) and those who were hospitalized with dengue hemorrhagic fever (hDHF, n=4). In contrast, responses in cultured ELISPOT assays were more reliably detectable prior to secondary infection and showed more consistent increases after infection. Responses in cultured ELISPOT assays were higher in individuals with hDHF (n=8) compared to NH (n=9) individuals before the secondary infection, with no difference between these groups after infection. These data demonstrate an association of pre-existing DENV-specific memory responses with the severity of illness in subsequent DENV infection, and suggest that frequencies of DENV-reactive T cells measured after short-term culture may be of particular importance for assessing the risk for more severe dengue disease.

scholarly journals SARS-CoV-2-specific T Cell Memory is Sustained in COVID-19 Convalescents for 8 Months with Successful Development of Stem Cell-like Memory T Cells

2021 ◽  
Author(s):  
Jae Hyung Jung ◽  
Min-Seok Rha ◽  
Moa Sa ◽  
Hee Kyoung Choi ◽  
Ji Hoon Jeon ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Memory T Cells ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Mhc I ◽  
Cell Responses ◽  
Proliferation Capacity ◽  
Specific Memory

AbstractMemory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. We conducted direct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescents up to 254 days post-symptom onset (DPSO). Here, we report that memory T cell responses were maintained during the study period. In particular, we observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells increased, peaking at approximately 120 DPSO. Development of TSCM cells was confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19. The current study provides insight for establishing an effective vaccination program and epidemiological measurement.

scholarly journals Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1490
Author(s):  
Victoria Matyushenko ◽  
Irina Isakova-Sivak ◽  
Igor Kudryavtsev ◽  
Arina Goshina ◽  
Anna Chistyakova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Natural Infection ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

scholarly journals Ex Vivo Phenotype and Frequency of Influenza Virus-Specific CD4 Memory T Cells

2004 ◽  
Vol 78 (13) ◽  
pp. 7284-7287 ◽  
Author(s):  
Michaela Lucas ◽  
Cheryl L. Day ◽  
Jessica R. Wyer ◽  
Sharon L. Cunliffe ◽  
Andrew Loughry ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Ex Vivo ◽  
Class Ii ◽  
Low Frequencies ◽  
Tetramer Staining ◽  
Specific Memory ◽  
Memory Cd4 T Cells

ABSTRACT Recent advances in class II tetramer staining technology have allowed reliable direct ex vivo visualization of antigen-specific CD4 T cells. In order to define the frequency and phenotype of a prototype response to a nonpersistent pathogen, we have used such techniques to analyze influenza virus-specific memory CD4 T cells directly from blood. These responses are stably detectable ex vivo at low frequencies (range, 0.00012 to 0.0061% of CD4 T cells) and display a distinct “central memory” CD62L+ phenotype.

scholarly journals CD4 memory T cells survive and proliferate but fail to differentiate in the absence of CD40

2006 ◽  
Vol 203 (4) ◽  
pp. 897-906 ◽  
Author(s):  
Megan MacLeod ◽  
Mark J. Kwakkenbos ◽  
Alison Crawford ◽  
Sheila Brown ◽  
Brigitta Stockinger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Memory Cells ◽  
Cell Stage ◽  
Effector Cells ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Specific Memory

Secondary T cell responses are enhanced because of an expansion in numbers of antigen-specific (memory) cells. Using major histocompatibility complex class II tetramers we have tracked peptide-specific endogenous (non–T cell receptor transgenic) CD4 memory T cells in normal and in costimulation-deficient mice. CD4 memory T cells were detectable after immunization for more than 200 days, although decay was apparent. Memory cells generated in CD40 knockout mice by immunization with peptide-pulsed wild-type dendritic cells survived in the absence of CD40 and proliferated when boosted with peptide (plus adjuvant) in a CD40-independent fashion. However, differentiation of the memory cells into cytokine-producing effector cells did not occur in the absence of CD40. The data indicate that memory cells can be generated without passing through the effector cell stage.

scholarly journals Persistent Cellular Immunity to SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Gaëlle Breton ◽  
Pilar Mendoza ◽  
Thomas Hagglof ◽  
Thiago Y. Oliveira ◽  
Dennis Schaefer-Babajew ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Division ◽  
T Cell ◽  
T Cell Responses ◽  
Memory T Cell ◽  
Cell Responses ◽  
Paired Samples ◽  
Specific Memory ◽  
Immune Alterations

AbstractSARS-CoV-2 is responsible for an ongoing pandemic that affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 months after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen specific memory that could contribute to rapid recall responses. In addition, recovered individuals show enduring immune alterations in relative numbers of CD4+ and CD8+ T cells, expression of activation/exhaustion markers, and cell division.SummaryWe show that SARS-CoV-2 infection elicits broadly reactive and highly functional memory T cell responses that persist 6 months after infection. In addition, recovered individuals show enduring immune alterations in CD4+ and CD8+ T cells compartments.

scholarly journals Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Nathan Schoettler ◽  
Cara L Hrusch ◽  
Kelly M Blaine ◽  
Anne I Sperling ◽  
Carole Ober
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Lung ◽  
Memory T Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Memory T Cell ◽  
Specific Memory

Abstract Antigen-specific memory T cells persist for years after exposure to a pathogen and provide effective recall responses. Many memory T cell subsets have been identified and differ in abundance throughout tissues. This study focused on CD4 and CD8 memory T cells from paired human lung and lung draining lymph node (LDLN) samples and identified substantial differences in the transcriptional landscape of these subsets, including higher expression of an array of innate immune receptors in lung T cells which were further validated by flow cytometry. Using T cell receptor analysis, we determined the clonal overlap between memory T cell subsets within the lung and within the LDLN, and this was greater than the clonal overlap observed between memory T cell subsets compared across tissues. Our results suggest that lung and LDLN memory T cells originate from different precursor pools, recognize distinct antigens and likely have separate roles in immune responses.

scholarly journals Regulation of Cytokine Production by Virus-Specific CD8 T Cells in the Lungs

2008 ◽  
Vol 82 (16) ◽  
pp. 7799-7811 ◽  
Author(s):  
Ross B. Fulton ◽  
Matthew R. Olson ◽  
Steven M. Varga
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
Memory T Cells ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Lung Parenchyma ◽  
Host Cells ◽  
Peripheral Tissues ◽  
Specific Memory

ABSTRACT Inflammation and the elimination of infected host cells during an immune response often cause local tissue injury and immunopathology, which can disrupt the normal functions of tissues such as the lung. Here, we show that both virus-induced inflammation and the host tissue environment combine to influence the capacity of virus-specific CD4 and CD8 T cells to produce cytokines in various tissues. Decreased production of cytokines, such as IFN-γ and TNF-α, by antigen-specific T cells is more pronounced in peripheral tissues, such as the lung and kidney, than in secondary lymphoid organs, such as the spleen or lymph nodes. We also demonstrate that tissues regulate cytokine production by memory T cells independently of virus infection, as memory T cells that traffic into the lungs of naïve animals exhibit a reduced ability to produce cytokines following direct ex vivo peptide stimulation. Furthermore, we show that cytokine production by antigen-specific memory CD4 and CD8 T cells isolated from the lung parenchyma can be rescued by stimulation with exogenous peptide-pulsed antigen-presenting cells. Our results suggest that the regulation of T-cell cytokine production by peripheral tissues may serve as an important mechanism to prevent immunopathology and preserve normal tissue function.

scholarly journals Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen.

1995 ◽  
Vol 181 (5) ◽  
pp. 1935-1940 ◽  
Author(s):  
L F Santamaria Babi ◽  
L J Picker ◽  
M T Perez Soler ◽  
K Drzimalla ◽  
P Flohr ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
Memory T Cells ◽  
Homing Receptor ◽  
Memory T Cell ◽  
Cell Responses ◽  
Allergic Contact

The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for the vascular adhesion molecule E-selectin, and it has been proposed to be involved in the selective targeting of memory T cells reactive with skin-associated Ag to cutaneous inflammatory sites. To further investigate the relation of CLA and cutaneous T cell responses, we analyzed the CLA phenotype of circulating memory T cells in patients with allergic contact dermatitis and atopic dermatitis (AD) alone vs in patients manifesting bronchopulmonary atopy (asthma with or without AD) and nonallergic individuals. Significant T cell proliferative responses to Ni, a contact allergen, and to the house dust mite (HDM), an allergen to which sensitization is often observed in AD and/or asthma, was noted only in allergic and atopic individuals, respectively. When the minor circulating CLA+CD3+CD45RO+ subset was separated from the major CLA-CD3+CD45RO+ subpopulation in Ni-sensitive subjects, the Ni-dependent memory T cell response was largely confined to the CLA+ subset. A similar restriction of the T cell proliferative response to the CLA+ memory subset was observed for HDM in patients with AD alone. In HDM-sensitive patients with asthma with or without AD, however, the CLA- subset exhibited a strong antigen-dependent proliferation, in contrast to patients with AD alone, whose CLA- subset proliferated very weakly to HDM. In asthma with or without AD, the HDM-dependent proliferation slightly predominated in the CLA- when compared to the CLA+ subset. The functional linkage between CLA expression and disease-associated T cell effector function in AD was also demonstrated by the finding that the circulating CLA+ T cell subset in AD patients, but not nonatopic controls, selectively showed both evidence of prior activation (human histocompatibility antigen-DR expression) and spontaneous production of interleukin 4 but not interferon-gamma. Taken together, these observations demonstrate the correlation of CLA expression on circulating memory T cells and disease-associated memory T cell responses in cutaneous hypersensitivity, and they suggest the existence of mechanisms capable of sorting particular T cell Ag specificities and lymphokine patterns into homing receptor-defined memory subsets.

scholarly journals The transfer of adaptive immunity to CMV during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor

Blood ◽  
2009 ◽  
Vol 114 (24) ◽  
pp. 5071-5080 ◽  
Author(s):  
Phillip Scheinberg ◽  
Jan J. Melenhorst ◽  
Jason M. Brenchley ◽  
Brenna J. Hill ◽  
Nancy F. Hensel ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Memory T Cells ◽  
Viral Reactivation ◽  
Hematopoietic Stem ◽  
Cell Responses ◽  
Specific Memory

Abstract The successful reconstitution of adaptive immunity to human cytomegalovirus (CMV) in hematopoietic stem cell transplantation (HSCT) recipients is central to the reduction of viral reactivation-related morbidity and mortality. Here, we characterized the magnitude, specificity, phenotype, function, and clonotypic composition of CMV-specific T-cell responses in 18 donor-recipient pairs both before and after HSCT. The principal findings were: (1) the specificity of CMV-specific T-cell responses in the recipient after HSCT mirrors that in the donor; (2) the maintenance of these targeting patterns reflects the transfer of epitope-specific T-cell clonotypes from donor to recipient; (3) less differentiated CD27+CD57− CMV-specific memory T cells are more likely to persist in the recipient after HSCT compared with more terminally differentiated CD27− CD57+ CMV-specific memory T cells; (4) the presence of greater numbers of less differentiated CD8+ CMV-specific T cells in the donor appears to confer protection against viral reactivation in the recipient after HSCT; and (5) CMV-specific T cells acquire a more differentiated phenotype and a restricted functional profile after HSCT. Overall, these findings define the immunologic factors that influence the successful adoptive transfer of antigen-specific T-cell immunity during HSCT, which enables the identification of recipients at particular risk of CMV reactivation after HSCT.

scholarly journals Multimodal memory T cell profiling identifies a reduction in a polyfunctional Th17 state associated with tuberculosis progression

2020 ◽  
Author(s):  
Aparna Nathan ◽  
Jessica I. Beynor ◽  
Yuriy Baglaenko ◽  
Sara Suliman ◽  
Kazuyoshi Ishigaki ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Ex Vivo ◽  
Surface Proteins ◽  
Effector Memory ◽  
Specific Cell ◽  
Memory State ◽  
Memory T Cell ◽  
Cell State

AbstractMycobacterium tuberculosis (M.tb) results in 10 million active tuberculosis (TB) cases and 1.5 million deaths each year1, making it the world’s leading infectious cause of death2. Infection leads to either an asymptomatic latent state or TB disease. Memory T cells have been implicated in TB disease progression, but the specific cell states involved have not yet been delineated because of the limited scope of traditional profiling strategies. Furthermore, immune activation during infection confounds underlying differences in T cell state distributions that influence risk of progression. Here, we used a multimodal single-cell approach to integrate measurements of transcripts and 30 functionally relevant surface proteins to comprehensively define the memory T cell landscape at steady state (i.e., outside of active infection). We profiled 500,000 memory T cells from 259 Peruvians > 4.7 years after they had either latent M.tb infection or active disease and defined 31 distinct memory T cell states, including a CD4+CD26+CD161+CCR6+ effector memory state that was significantly reduced in patients who had developed active TB (OR = 0.80, 95% CI: 0.73–0.87, p = 1.21 × 10−6). This state was also polyfunctional; in ex vivo stimulation, it was enriched for IL-17 and IL-22 production, consistent with a Th17-skewed phenotype, but also had more capacity to produce IFNγ than other CD161+CCR6+ Th17 cells. Additionally, in progressors, IL-17 and IL-22 production in this cell state was significantly lower than in non-progressors. Reduced abundance and function of this state may be an important factor in failure to control M.tb infection.

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