scholarly journals Loss of Immunization-Induced Epitope-Specific CD4 T-Cell Response following Anaplasma marginale Infection Requires Presence of the T-Cell Epitope on the Pathogen and Is Not Associated with an Increase in Lymphocytes Expressing Known Regulatory Cell Phenotypes

2015 ◽  
Vol 22 (7) ◽  
pp. 742-753 ◽  
Author(s):  
Wendy C. Brown ◽  
Joshua E. Turse ◽  
Paulraj K. Lawrence ◽  
Wendell C. Johnson ◽  
Glen A. Scoles ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cell Epitope ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Γδ T Cell ◽  
Content Type ◽  
Cell Responses

ABSTRACTWe have shown that in cattle previously immunized with outer membrane proteins, infection withAnaplasma marginaleinduces a functionally exhausted CD4 T-cell response to theA. marginaleimmunogen. Furthermore, T-cell responses following infection in nonimmunized cattle had a delayed onset and were sporadic and transient during persistent infection. The induction of an exhausted T-cell response following infection presumably facilitates pathogen persistence. In the current study, we hypothesized that the loss of epitope-specific T-cell responses requires the presence of the immunizing epitope on the pathogen, and T-cell dysfunction correlates with the appearance of regulatory T cells. In limited studies in cattle, regulatory T cells have been shown to belong to γδ T-cell subsets rather than be CD4 T cells expressing forkhead box protein P3 (FoxP3). Cattle expressing the DRB3*1101 haplotype were immunized with a truncatedA. marginalemajor surface protein (MSP) 1a that contains a DRB3*1101-restricted CD4 T-cell epitope, F2-5B. Cattle either remained unchallenged or were challenged withA. marginalebacteria that express the epitope or withA. marginalesubsp.centralethat do not. Peripheral blood and spleen mononuclear cells were monitored for MSP1a epitope F2-5B-specfic T-cell proliferative responses and were stained for γδ T-cell subsets or CD4+CD25+FoxP3+T cells before and during infection. As hypothesized, the induction of T-cell exhaustion occurred only following infection withA. marginale, which did not correlate with an increase in either CD4+CD25+FoxP3+T cells or any γδ T-cell subset examined.

scholarly journals AChlamydia trachomatisStrain Expressing Ovalbumin Stimulates an Antigen-Specific CD4+T Cell Response in Mice

2019 ◽  
Vol 87 (7) ◽  
Author(s):  
Jennifer D. Helble ◽  
Michael N. Starnbach
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Fluorescent Protein ◽  
Genetic Manipulation ◽  
Cell Epitope ◽  
T Cell Response ◽  
Developmental Cycle ◽  
Dependent Manner ◽  
Content Type

ABSTRACTAntigen-specific CD4+T cells againstChlamydiaare crucial for driving bacterial clearance and mediating protection against reinfection. Although theChlamydia trachomatisprotein Cta1 has been identified to be a dominant murine CD4+T cell antigen, its level of expression during the bacterial developmental cycle and precise localization within the host cell are unknown. Newly developed tools forChlamydiagenetic manipulation have allowed us to generate aC. trachomatisstrain expressing a heterologous CD4+T cell epitope from ovalbumin (OVA) consisting of OVA residues 323 to 339 (OVA323–339). By tagging proteins expressed inC. trachomatiswith OVA323–339, we can begin to understand how protein expression, developmental regulation, and subcellular compartmentalization affect the potential of those proteins to serve as antigens. When OVA323–339was expressed as a fusion with green fluorescent protein, we found that we were able to elicit an OT-II T cell response in an antigen-dependent manner, but surprisingly, these T cells were unable to reduce bacterial burden in mice. These data suggest that the subcellular localization of antigen, the level of antigen expression, or the timing of expression within the developmental cycle ofChlamydiamay play a crucial role in eliciting a protective CD4+T cell response.

T Cell Recognition of HCMV: Pan-Genome Analysis of Immunogenic Open-Reading Frames.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 606-606 ◽  
Author(s):  
Louis J. Picker ◽  
Andrew W. Sylwester ◽  
Bridget L. Mitchell ◽  
Cara Taormina ◽  
Christian Pelte ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cell Response ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses

Abstract Human Cytomegalovirus (HCMV) is among the largest and most complex of known viruses with 150–200nm virions enclosing a double stranded 230kb DNA genome capable of coding for >200 proteins. HCMV infection is life-long, and for the vast majority of immune competent individuals clinically benign. Disease occurs almost exclusively in the setting of immune deficiency, suggesting that the stable host-parasite relationship that characterizes these infections is the result of an evolutionarily “negotiated” balance between viral mechanisms of pathogenesis and the host immune response. In keeping with, and perhaps because of this balance, the human CD4+ T cell response to whole HCMV viral lysates is enormous, with median peripheral blood frequencies of HCMV-specific cells ~5–10 fold higher than for analogous preparations of other common viruses. Although certain HCMV ORFs have been identified as targets of either the CD4+ or CD8+ T cell response, the specificities comprising the CD4+ T cell response, and both the total frequencies and component parts of the CD8+ T cell response are unknown. Here, we used cytokine flow cytometry and ~14,000 overlapping 15mer peptides comprising all 213 HCMV ORFs encoding proteins >100 amino acids in length to precisely define the total CD4+ and CD8+ HCMV-specific T cell responses and the HCMV ORFs responsible for these responses in 33 HCMV-seropositive, HLA-disparate donors. An additional 9 HCMV seronegative donors were similarly examined to define the extent to which non-HCMV responses cross-react with HCMV-encoded epitopes. We found that when totaled, the median frequencies of HCMV-specific CD4+ and CD8+ T cells in the peripheral blood of the seropositive subjects were 4.0% and 4.5% for the total CD4+ or CD8+ T cell populations, respectively (which corresponds to 9.1% and 10.5% of the memory populations, respectively). The HCMV-specific CD4+ and CD8+ T cell responses included a median 12 and 7 different ORFs, respectively, and all told, 73 HCMV ORFs were identified as targets for both CD4+ and CD8+ T cells, 26 ORFs as targets for CD8+ T cells alone, and 43 ORFS as targets for CD4+ T cells alone. UL55, UL83, UL86, UL99, and UL122 were the HCMV ORFs most commonly recognized by CD4+ T cells; UL123, UL83, UL48, UL122 and UL28 were the HCMV ORFs most commonly recognized by CD8+ T cells. The relationship between immunogenicity and 1) HLA haplotype and 2) ORF expression and function will be discussed. HCMV-seronegative individuals were non-reactive with the vast majority of HCMV peptides. Only 7 potentially cross-reactive responses were identified (all by CD8+ T cells) to 3 ORFs (US32, US29 and UL116) out of a total of almost 4,000 potential responses, suggesting fortuitous cross-reactivity with HCMV epitopes is uncommon. These data provide the first glimpse of the total human T cell response to a complex infectious agent, and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.

scholarly journals Suppression of viral specific primary T-cell response following intense physical exercise in young but not old mice

2005 ◽  
Vol 98 (2) ◽  
pp. 663-671 ◽  
Author(s):  
Zoher F. Kapasi ◽  
Michael L. McRae ◽  
Rafi Ahmed
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Exhaustive Exercise ◽  
Cd4 T Cell ◽  
Intense Exercise ◽  
Expansion Phase ◽  
Cell Responses ◽  
Old Mice

Intense exercise to exhaustion leads to increased susceptibility and severity of infections. T cells play an essential role in control of viral infections. Whereas immune suppression is considered as a likely mechanism for exhaustive exercise-induced susceptibility to infection, we know little about viral-specific T-cell response following exhaustive exercise in young or old mice. In this study, one group of female young (10–12 wk) and old (22–24 mo) C57BL/6 mice was exposed to a single bout of intense exercise to exhaustion and immediately infected with lymphocytic choriomeningitis virus (LCMV). Eight days later, at the peak of expansion phase of T-cell response, we used tetramers of MHC class I molecules containing viral peptides to directly visualize antigen-specific CD8 T cells and a sensitive functional assay measuring interferon-γ production at the single-cell level to quantitate the CD8 and CD4 T-cell response. To evaluate the impact of intense exercise during both the initiation and evolution of the expansion phase of the T-cell response, a second group of young and old mice continued their daily bouts of intense exercise to exhaustion over the next 8 days. Our data show that, in young mice, LCMV infection following exhaustive exercise leads to suppression of LCMV-specific CD8 and CD4 T-cell responses, and this suppression effect occurs at the initiation of the expansion phase of viral-specific T cells. However, in old mice, unlike young mice, exhaustive exercise does not cause suppression of LCMV-specific T-cell responses.

scholarly journals Promotion of a Subdominant CD8 T Cell Response during Murine Gammaherpesvirus 68 Infection in the Absence of CD4 T Cell Help

2014 ◽  
Vol 88 (14) ◽  
pp. 7862-7869 ◽  
Author(s):  
Michael L. Freeman ◽  
Alan D. Roberts ◽  
Claire E. Burkum ◽  
David L. Woodland ◽  
Marcia A. Blackman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Cd4 T Cell Help ◽  
T Cell Help

ABSTRACTCD8 and CD4 T cells are each critically important for immune control of murine gammaherpesvirus 68 (γHV68) infection. In immunocompetent mice, acute γHV68 infection results in lifelong latency, but in the absence of CD4 T cell help, mice succumb to viral recrudescence and disease. However, the requirements for CD4 T cell help in the generation and maintenance of antiviral CD8 T cell responses are incompletely understood, and it is unclear whether there are epitope-specific differences in the requirement of CD8 T cells for CD4 help. In this report, we characterized the CD8 T cell response to γHV68 in major histocompatibility complex (MHC) class II−/−mice, which lack CD4 T cells, or after antibody-mediated depletion of CD4 T cells. All antiviral CD8 T cells exhibited marked upregulation of surface expression of the inhibitory receptor programmed death-1 (PD-1), but surprisingly, while the immunodominant memory response appeared to be functionally impaired, helpless CD8 T cells of a subdominant specificity had increased numbers and enhanced functionality. Thus, we demonstrate differential requirements for CD4 help in the antiviral CD8 T cell response to a latent gammaherpesvirus.IMPORTANCEγHV68 is a mouse pathogen closely related to the oncogenic human γHVs, which infect a majority of the world's population. Reactivation of these viruses from latency can lead to complications, disease, and even death. CD4 T cells are required for complete immune control of long-term infection, in part by providing key signals to dendritic cells that in turn instruct optimal antiviral CD8 T cell responses. We have investigated multiple virus-specific CD8 T cell responses during infection and identified a subdominant CD8 T cell response that is numerically and functionally enhanced in the absence of CD4 T cell help. This occurs in spite of high surface expression of an inhibitory receptor and in contrast to the immunodominant response, which is impaired. Our data suggest that signals from CD4 T cells are important in maintaining the CD8 T cell hierarchy during γHV infections.

Analysis of EBV-Specific T Cell Responses in Transplant Recipients with PTLD.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1915-1915
Author(s):  
Kathrin Sebelin ◽  
Antje Meier ◽  
Matthias Papp-Vary ◽  
Stefan Oertel ◽  
Antonio Pezzutto ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Cell Response ◽  
Low Frequency ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Responses

Abstract EBV causes a chronic infection in >95 % of the population and despite its strong growth transforming capacity the majority of EBV infected individuals remain asymptomatic. In contrary, in immunosuppressed patients (pts) the risk of EBV reactivation and development of posttransplant lymphoproliferative disease (PTLD) is high. This is assumed to be due to a defective T cell response. Here we analyzed the EBV-specific CD8 and CD4 T cell response to different EBV latent and lytic antigens in pts with newly diagnosed PTLD. A prospective study of 10 pts after solid organ transplantation at time of diagnosis of PTLD was performed. EBV-specific CD8 T cells were examined by flow cytometric analysis using HLA-A2, HLA-B7 and HLA-B8 restricted tetramers incorporating BMLF1 (lytic), EBNA3 and LMP2 (both latent)-derived peptides. Staining was done in conjunction with mAbs against CD8 and CCR7. The ability of CD8 T cells to produce IFN-γ in response to the same EBV-derived peptides was measured by cytokine secretion assay. In healthy, EBV+ donors, we previously have found a consistent CD4 T cell response to the latent EBV antigen EBNA1. Therefore, EBNA1-specific CD4 T cell responses were monitored for IFN-g / IL-4 secretion after protein stimulation. T cell analysis was combined with EBV-DNA quantiation by real time PCR. We found EBV-specific CD8 T cell responses at low frequency in most pts with PTLD (8/10). Half of the pts showed low frequency EBNA1 specific CD4+ T cell responses. All pts with an EBNA1 specific CD4 T cell response showed an EBV-specific CD8 T cell response. In 2/10 pts we found no EBV-specific CD4 and CD8 T cell responses and both pts died under initial therapy. EBV-viral load was found to inversely correlate to absolute CD4 T cell counts. In comparison to healthy normal donors, no significant differences in EBV-specific T cell response could be observed. However, pts EBV-specific T cells were decreased in comparison to pts with high EBV viral load after TX and no PTLD as well as in comparison to pts with infectious mononucleosis. These results indicate that impairment of EBV-specific T cells is not due to clonal depletion, but rather seems to be due to impaired functional activation and expansion. We therefore conclude that pts with PTLD have an inadequatly low EBV-specific T cell responses which correlates to a low absolute CD4 T cell count. We propose a combined immunomonitoring of EBV viral load, absolute CD4 T cell count and EBV-specific T cell enumeration in pts at risk for development of PTLD. Further studies are needed to evaluate the role of EBV-specific T cell monitoring in immunosuppressed pts for prediction of PTLD and the potential usefulness of T cell monitoring as a prognostic marker in PTLD.

Analysis of HIV-1–  and CMV-specific memory CD4 T-cell responses during primary and chronic infection

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1381-1387 ◽  
Author(s):  
Alexandre Harari ◽  
G. Paolo Rizzardi ◽  
Kim Ellefsen ◽  
Donatella Ciuffreda ◽  
Patrick Champagne ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cmv Infection ◽  
Cell Responses ◽  
Specific Memory ◽  
Hiv 1

CD4 T-cell–specific memory antiviral responses to human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) were investigated in 16 patients with documented primary HIV-1 infection (4 of the 16 subjects also had primary CMV infection) and compared with those observed in patients with chronic HIV-1 and CMV coinfection. Virus-specific memory CD4 T cells were characterized on the basis of the expression of the chemokine receptor CCR7. HIV-1– and CMV-specific interferon-γ–secreting CD4 T cells were detected in patients with primary and chronic HIV-1 and CMV coinfection and were mostly contained in the cell population lacking expression of CCR7. The magnitude of the primary CMV-specific CD4 T-cell response was significantly greater than that of chronic CMV infection, whereas there were no differences between primary and chronic HIV-1–specific CD4 T-cell responses. A substantial proportion of CD4+CCR7− T cells were infected with HIV-1. These results advance the characterization of antiviral memory CD4 T-cell response and the delineation of the potential mechanisms that likely prevent the generation of a robust CD4 T-cell immune response during primary infection.

scholarly journals The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

2012 ◽  
Vol 80 (9) ◽  
pp. 3279-3288 ◽  
Author(s):  
Harshita Satija Grover ◽  
Nicolas Blanchard ◽  
Federico Gonzalez ◽  
Shiao Chan ◽  
Ellen A. Robey ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
Mhc Class Ii ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Parasite Burden ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Content Type

ABSTRACTThe apicomplexan parasiteToxoplasma gondiican cause severe disease in immunocompromised individuals. Previous studies in mice have focused largely on CD8+T cells, and the role of CD4 T cells is relatively unexplored. Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response. To identify the CD4 T cell-stimulating antigens, we generated aT. gondii-specific,lacZ-inducible, CD4 T cell hybridoma and used it as a probe to screen aT. gondiicDNA library. We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells. Immunization of mice with the AS15 peptide provided significant protection against subsequent parasite challenge, resulting in a lower parasite burden in the brain. Our findings identify the first CD4 T cell-stimulating peptide that can confer protection against toxoplasmosis and provide an important tool for the study of CD4 T cell responses and the design of effective vaccines against the parasite.

scholarly journals CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation

2020 ◽  
Author(s):  
Hassen Kared ◽  
Andrew D Redd ◽  
Evan M Bloch ◽  
Tania S. Bonny ◽  
Hermi Sumatoh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Inflammatory Responses ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cross Sectional ◽  
Cell Responses

AbstractCharacterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

Cytomegalovirus-Specific T Cells Are Elicited Early After Umbilical Cord Blood Transplant but Fail to Expand In Vivo and Control Virus Replication

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1974-1974
Author(s):  
Suzanne M. McGoldrick ◽  
Abraham Guerrero ◽  
Tori N. Yamamoto ◽  
Colleen Delaney ◽  
Stanley R. Riddell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Time Points ◽  
Cell Responses ◽  
Ifn Γ

Abstract Abstract 1974 Cytomegalovirus (CMV) is a major infectious complication in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and has been linked to deficiencies of virus-specific T cell immunity. Compared to bone marrow or peripheral blood stem cell transplants, recipients of single or double umbilical cord blood transplants (UCBT) receive lower numbers of donor T cells that have not previously been primed to CMV and are at increased risk for early and recurrent CMV infections. At our institution, the rate of CMV reactivation in CMV seropositive patients undergoing CBT is close to 100% with standard dose Acyclovir as prophylaxis [Delaney unpublished data]. Here, we systematically analyzed the kinetics of recovery, durability, and specificity of CMV-specific CD8+ and CD4+ T cell responses in UCBT recipients. CD8 T cell responses to CMV were analyzed by interferon γ (IFN-γ) intracellular cytokine staining after stimulating recipient peripheral blood mononuclear cells (PBMC) obtained at various time points after CBT with autologous patient fibroblasts infected with the RV798 virus, which is a mutant CMV strain that lacks the viral US genes that downregulate class I MHC and can present all potentially immunogenic epitopes of the virus. The mean absolute CD8 T cell counts were 59, 93 and 213 cells/μl and the mean CD4 T cell counts were 154, 223 and 397 cells/μl in PBMC at day 56, 180 and 365 respectively. Direct assays of PBMC after a 4–6 hour stimulation with RV798-infected fibroblasts did not detect a significant frequency of IFN-γ+ CD8+ T cells in CBT recipients, in contrast to normal CMV+ donors that exhibited frequencies of CD8+ T cells of 2–10%. However, IFN-γ+ CMV specific CD8 T cells were readily detectable in PBMC obtained as early as day 42 after UCBT from 8 out of 8 CMV positive CBT recipients after a 10 day stimulation with RV798 infected fibroblasts. These responses were sustained at multiple time points through day 365 post transplant. This result was not a consequence of in vitro priming of CD8 T cells by prolonged stimulation with RV798 since we did not detect a CMV-specific T cell response in 3 out of 3 CMV seronegative recipients at any time through day 365 with the same assay. To assess CD4+ T cell responses, we performed lymphoproliferative assays (LPA) by stimulating patient PBMC obtained at the same time points with whole CMV antigen. The proportion of patients with a positive response at day 56, 80, 180 and 365 was 0.38, 0.50, 0.88, and 1.0 respectively. All of the CMV positive CBT recipients in our study had multiple occurrences of CMV reactivation throughout the first year post CBT requiring antiviral drug therapy. The CMV-specific CD8 T cell response in normal CMV+ individuals recognizes a large number of distinct dominant and subdominant antigens and a potential explanation for the failure to control CMV after CBT is that the T cell response may not be sufficiently diverse. We analyzed the specificity of CMV specific CD8+ T cells that developed after CBT in 4 recipients by assessing recognition of COS cells transfected with the class I HLA restricting alleles and with a CMV plasmid library consisting of 142 ORFs, subdivided into pools. A response was seen in 3 out of 4 patients to at least 3 different CMV antigens by day 80 post CBT, including previously defined dominant epitopes in pp65 and this diversity was maintained through 6–12 months post transplant. One patient had a less diverse response early post CBT and the response changed over time to include recognition of new epitopes. Collectively, our results demonstrate that CD8+ and CD4+ T cells are primed to CMV antigens very early after CBT despite the infusion of limited numbers of naïve T cells and the administration of post transplant immunosuppression. The inability to control CMV infection may be due to a quantitative deficiency of CMV-specific T cells resulting from the inability of CMV-specific T cells to expand in vivo to numbers sufficient to eliminate virus replication. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antigen persistence is required throughout the expansion phase of a CD4+ T cell response

2005 ◽  
Vol 201 (10) ◽  
pp. 1555-1565 ◽  
Author(s):  
Reinhard Obst ◽  
Hisse-Martien van Santen ◽  
Diane Mathis ◽  
Christophe Benoist
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Cd4 T Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Expansion Phase ◽  
Antigen Persistence

For CD8+ T cells, a relatively short antigen pulse seems sufficient for antigen-presenting cells to drive clonal expansion and differentiation. It is unknown whether the requirement for antigen is similarly ephemeral for CD4+ T cells. To study the dependence of a CD4+ T cell response on antigen persistence in a quantitatively and temporally controlled manner in vivo, we engineered a mouse line expressing a major histocompatibility complex class II–restricted epitope in dendritic cells under the control of a tetracycline-inducible promoter. Experiments tracking the proliferation of CD4+ T cells exposed to their cognate antigen in various amounts for different time periods revealed that the division of such cells was contingent on the presence of antigen throughout their expansion phase, even in the presence of an inflammatory stimulus. This previously unrecognized feature of a CD4+ T cell response contrasts with the proliferative behavior of CD8+ T cells that has been documented, and it implies that the two T cell subsets might require different strategies for efficient vaccination.

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