Outline Extraction with Question-Specific Memory Cells

2020 ◽  
Vol 19 (4) ◽  
pp. 1-17
Author(s):  
Jingxuan Yang ◽  
Haotian Cui ◽  
Si Li ◽  
Sheng Gao ◽  
Jun Guo ◽  
...  
Keyword(s):  
Memory Cells ◽  
Specific Memory ◽  
Outline Extraction

scholarly journals HIV-1 Viremia Prevents the Establishment of Interleukin 2–producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity

2003 ◽  
Vol 198 (12) ◽  
pp. 1909-1922 ◽  
Author(s):  
Souheil-Antoine Younes ◽  
Bader Yassine-Diab ◽  
Alain R. Dumont ◽  
Mohamed-Rachid Boulassel ◽  
Zvi Grossman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Memory Cells ◽  
Cell Responses ◽  
Specific Memory ◽  
Ifn Γ ◽  
Memory Cd4 T Cells

CD4+ T cell responses are associated with disease control in chronic viral infections. We analyzed human immunodeficiency virus (HIV)-specific responses in ten aviremic and eight viremic patients treated during primary HIV-1 infection and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)-carboxyfluorescein diacetate-succinimidyl ester–based proliferation assay, we observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory CD4+ T cells were identified in aviremic patients, CD45RA− CCR7+ central memory cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA− CCR7− effector memory cells (Tem) that produced both IL-2 and interferon (IFN)-γ. In contrast, in viremic, therapy-failing patients, we found significant frequencies of Tem that unexpectedly produced exclusively IFN-γ. Longitudinal analysis of HIV epitope–specific CD4+ T cells revealed that only cells that had the capacity to produce IL-2 persisted as long-term memory cells. In viremic patients the presence of IFN-γ–producing cells was restricted to periods of elevated viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2–producing CD4+ T cells and that IFN-γ only–producing cells are short lived. Our data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-γ only–producing cells that lack self-renewal capacity.

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 Antigenic Restimulation of Virus-Specific Memory CD8+ T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic Capacity

2020 ◽  
Vol 94 (23) ◽  
Author(s):  
Stephen A. Migueles ◽  
Daniel C. Rogan ◽  
Noah V. Gavil ◽  
Elizabeth P. Kelly ◽  
Sushila A. Toulmin ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Expression ◽  
Posttranscriptional Regulation ◽  
Granzyme B ◽  
Protein Accumulation ◽  
Mrna Levels ◽  
Memory Cells ◽  
Virus Infections ◽  
Prolonged Stimulation ◽  
Specific Memory

ABSTRACT In various infections or vaccinations of mice or humans, reports of the persistence and the requirements for restimulation of the cytotoxic mediators granzyme B (GrB) and perforin (PRF) in CD8+ T cells have yielded disparate results. In this study, we examined the kinetics of PRF and GrB mRNA and protein expression after stimulation and associated changes in cytotoxic capacity in virus-specific memory cells in detail. In patients with controlled HIV or cleared respiratory syncytial virus (RSV) or influenza virus infections, all virus-specific CD8+ T cells expressed low PRF levels without restimulation. Following stimulation, they displayed similarly delayed kinetics for lytic protein expression, with significant increases occurring by days 1 to 3 before peaking on days 4 to 6. These increases were strongly correlated with, but were not dependent upon, proliferation. Incremental changes in PRF and GrB percent expression and mean fluorescence intensity (MFI) were highly correlated with increases in HIV-specific cytotoxicity. mRNA levels in HIV-specific CD8+ T-cells exhibited delayed kinetics after stimulation as with protein expression, peaking on day 5. In contrast to GrB, PRF mRNA transcripts were little changed over 5 days of stimulation (94-fold versus 2.8-fold, respectively), consistent with posttranscriptional regulation. Changes in expression of some microRNAs, including miR-17, miR-150, and miR-155, suggested that microRNAs might play a significant role in regulation of PRF expression. Therefore, under conditions of extremely low or absent antigen levels, memory virus-specific CD8+ T cells require prolonged stimulation over days to achieve maximal lytic protein expression and cytotoxic capacity. IMPORTANCE Antigen-specific CD8+ T cells play a major role in controlling most virus infections, primarily by perforin (PRF)- and granzyme B (GrB)-mediated apoptosis. There is considerable controversy regarding whether PRF is constitutively expressed, rapidly increased similarly to a cytokine, or delayed in its expression with more prolonged stimulation in virus-specific memory CD8+ T cells. In this study, the degree of cytotoxic capacity of virus-specific memory CD8+ T cells was directly proportional to the content of lytic molecules, which required antigenic stimulation over several days for maximal levels. This appeared to be modulated by increases in GrB transcription and microRNA-mediated posttranscriptional regulation of PRF expression. Clarifying the requirements for maximal cytotoxic capacity is critical to understanding how viral clearance might be mediated by memory cells and what functions should be induced by vaccines and immunotherapies.

Persistence of High Viral Load Abrogates Long-Term HIV-Specific Memory CD4 T-Cells Producing Interleukin-2.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3104-3104
Author(s):  
Mohamed-Rachid Boulassel ◽  
Souheil-Antoine Younes ◽  
Bader Yacine-Diab ◽  
Rafick-Pierre Sekaly ◽  
Jean Pierre Routy
Keyword(s):  
Viral Load ◽  
Long Term Memory ◽  
Memory Cells ◽  
Cd4 Cells ◽  
Proliferating Cells ◽  
Term Memory ◽  
Cell Responses ◽  
Specific Memory ◽  
Ifn Γ

Abstract Virus-specific CD4 T-cells are believed to play a critical role in determining the persistence of memory and effector CD8 T-cell responses during viral infections. However, the reasons for which human immunodeficiency virus (HIV)-specific CD4 cells fail to generate effective CD8 cell responses remain incompletely understood. In this study, we analyzed the HIV-specific CD4 cells in 10 aviremic (viral load < 50 copies/ml) and 8 viremic (mean viral load 45,295 copies/ml) patients treated during primary HIV infection and followed for up to 6 years. At the time of apheresis, median CD4 T cell counts for aviremic and viremic patients were 671 cells/μl and 485 cells/μl respectively. Using Gag and Nef overlapping HIV peptides, the highly sensitive CFSE-based proliferation assay and intracellular staining techniques, we observed that proliferative Gag and Nef peptide-specific CD4 cell responses were 30-fold higher in aviremic patients compared to viremic. Several subsets of HIV-specific memory CD4 cells endowed with different proliferative and functional capacities were identified. We observed two subsets of HIV-specific memory CD4 cells in aviremic patients, CD45RA− CCR7+ central memory cells (Tcm) producing exclusively IL-2 and CD45RA− CCR7− effector memory cells (Tem) that produced both IL-2 and IFN-γ. In contrast, in viremic patients, Tem were found to unexpectedly produce IFN-γ exclusively. Longitudinal data showed that only cells, which were capable of producing IL-2, persisted as long-term memory cells. In viremic patients, HIV-specific CD4 cells that produce INF-γ were found only during periods of elevated viral loads. To test if the presence of IL-2 could restore the proliferation of these cells, we stimulated CD4 cells from viremic patients with a pool of peptides, which gave strong IFN-γ responses in these patients in the presence of exogenous IL-2. The addition of IL-2 during the in vitro peptide stimulation dramatically increased the fraction of proliferating cells. This experiment strongly suggests that the impaired proliferation of CD4 cells from viremic patients is not caused by a virus-mediated destruction of proliferating cells but a lack of producing IL-2. Altogether, these results indicate that long-term memory HIV-specific CD4 cell produce mainly IL-2, while those producing IFN-γ are short-lived. These findings favor a model in which Tcm are continuously produced in limited numbers but under continuous viral stimulation are rapidly induced to differentiate into IFN-γ only-producing cells that lack the capacity for self-renewal.These findings also indicate that treatment strategies aimed to increase the long-term memory CD4 cells are needed for future HIV vaccine development.

scholarly journals Complex Memory T-Cell Phenotypes Revealed by Coexpression of CD62L and CCR7

2005 ◽  
Vol 79 (7) ◽  
pp. 4510-4513 ◽  
Author(s):  
Heike Unsoeld ◽  
Hanspeter Pircher
Keyword(s):  
T Cells ◽  
Lymphocytic Choriomeningitis ◽  
Effector Memory ◽  
Memory Cells ◽  
Memory Cd8 T Cells ◽  
Memory T Cell ◽  
Specific Memory ◽  
Major Shift ◽  
T Cell Phenotypes ◽  
Cell Phenotypes

ABSTRACT Antigen-experienced T cells have been divided into CD62L+ CCR7+ central memory (TCM) and CD62L− CCR7− effector memory (TEM) cells. Here, we examined coexpression of CD62L and CCR7 in lymphocytic choriomeningitis virus-specific memory CD8 T cells from both lymphoid and nonlymphoid tissues. Three main points emerged: firstly, memory cells frequently expressed a mixed CD62L− CCR7+ phenotype that differed from the phenotypes of classical TEM and TCM cells; secondly, TCM cells were not restricted to lymphoid organs but were also present in significant numbers in nonlymphoid tissues; and thirdly, a major shift from a TCM to TEM phenotype was found in memory cells that had been stimulated repetitively with antigen.

scholarly journals DETERMINATION OF ANTIBODY CLASS IN A SYSTEM OF COOPERATING ANTIGENIC DETERMINANTS

1970 ◽  
Vol 132 (5) ◽  
pp. 1019-1034 ◽  
Author(s):  
Volker Schirrmacher ◽  
Klaus Rajewsky
Keyword(s):  
Secondary Response ◽  
Antigenic Determinants ◽  
Time Interval ◽  
Memory Cells ◽  
Class Distribution ◽  
Specific Memory ◽  
Antibody Induction ◽  
Antibody Class ◽  
Secondary Antibodies ◽  
Secondary Injection

19S and 7S memory is analyzed in a system of cooperating antigenic determinants. Cooperation occurs in the induction of both 19S and 7S secondary antibodies, and for both responses carrier specificity can be entirely accounted for by presensitization of the animal to carrier determinants. The class distribution of secondary anti-hapten antibody depends on the dose of the hapten primary-carrier conjugate used for priming, and on the time interval between priming with the hapten primary-carrier conjugate and secondary injection. The conditions of priming with the secondary carrier influence the extent of the secondary response but not the class distribution of secondary antibody. The data confirm the cooperation hypothesis of antibody induction. Specifically, we interpret them to mean that in hapten-carrier cooperation, the hapten-specific memory cells are predetermined for the class of the emerging antibodies. Together with the hapten-specific memory cells, the carrier-specific helpers are responsible for the extent of the secondary response.

scholarly journals Evidence for an Underlying CD4 Helper and CD8 T-Cell Defect in B-Cell-Deficient Mice: Failure To Clear Persistent Virus Infection after Adoptive Immunotherapy with Virus-Specific Memory Cells from μMT/μMT Mice

1998 ◽  
Vol 72 (11) ◽  
pp. 9208-9216 ◽  
Author(s):  
Dirk Homann ◽  
Antoinette Tishon ◽  
Dietmar P. Berger ◽  
William O. Weigle ◽  
Matthias G. von Herrath ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Adoptive Transfer ◽  
Cd8 T Cell ◽  
Memory Cells ◽  
Specific Memory ◽  
Persistent Virus ◽  
B Mice ◽  
Ifn Γ

ABSTRACT Adoptive transfer of virus-specific memory lymphocytes can be used to identify factors and mechanisms involved in the clearance of persistent virus infections. To analyze the role of B cells in clearing persistent infection with lymphocytic choriomeningitis virus (LCMV), we used B-cell-deficient μMT/μMT (B−/−) mice. B−/− mice controlled an acute LCMV infection with the same kinetics and efficiency as B-cell-competent (B+/+) mice via virus-specific, major histocompatibility complex (MHC) class I-restricted CD8+cytotoxic T lymphocytes (CTL). CTL from B−/− and B+/+ mice were equivalent in affinity to known LCMV CTL epitopes and had similar CTL precursor frequencies (pCTL). Adoptive transfer of memory cells from B+/+ mice led to virus clearance from persistently infected B+/+ recipients even after in vitro depletion of B cells, indicating that B cells or immunoglobulins are not required in the transfer population. In contrast, transfer of memory splenocytes from B−/− mice failed to clear virus. Control of virus was restored neither by transferring higher numbers of pCTL nor by supplementing B−/− memory splenocytes with LCMV-immune B cells or immune sera. Instead, B−/− mice were found to have a profound CD4 helper defect. Furthermore, compared to cultured splenocytes from B+/+ mice, those from B−/− mice secreted less gamma interferon (IFN-γ) and interleukin 2, with differences most pronounced for CD8 T cells. While emphasizing the importance of CD4 T-cell help and IFN-γ in the control of persistent infections, the CD4 T-helper and CD8 T-cell defects in B−/− mice suggest that B cells contribute to the induction of competent T effector cells.

scholarly journals New markers for murine memory B cells that define mutated and unmutated subsets

2007 ◽  
Vol 204 (9) ◽  
pp. 2103-2114 ◽  
Author(s):  
Shannon M. Anderson ◽  
Mary M. Tomayko ◽  
Anupama Ahuja ◽  
Ann M. Haberman ◽  
Mark J. Shlomchik
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Subset ◽  
Memory B Cells ◽  
Memory Cells ◽  
Pulse Label ◽  
Memory B Cell ◽  
Specific Memory ◽  
V Region ◽  
Different Origins

The study of murine memory B cells has been limited by small cell numbers and the lack of a definitive marker. We have addressed some of these difficulties with hapten-specific transgenic (Tg) mouse models that yield relatively large numbers of antigen-specific memory B cells upon immunization. Using these models, along with a 5-bromo-2′-deoxyuridine (BrdU) pulse-label strategy, we compared memory cells to their naive precursors in a comprehensive flow cytometric survey, thus revealing several new murine memory B cell markers. Most interestingly, memory cells were phenotypically heterogeneous. Particularly surprising was the finding of an unmutated memory B cell subset identified by the expression of CD80 and CD35. We confirmed these findings in an analogous V region knock-in mouse and/or in non-Tg mice. There also was anatomic heterogeneity, with BrdU+ memory cells residing not just in the marginal zone, as had been thought, but also in splenic follicles. These studies impact the current understanding of murine memory B cells by identifying new phenotypes and by challenging assumptions about the location and V region mutation status of memory cells. The apparent heterogeneity in the memory compartment implies either different origins and/or different functions, which we discuss.

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