The Initial Draining Lymph Node Primes the Bulk of the CD8 T Cell Response and Influences Memory T Cell Trafficking after a Systemic Viral Infection

Olson, Matthew R.; McDermott, Daniel S.; Varga, Steven M.

doi:10.1371/journal.ppat.1003054

Cited by 34 publications

(33 citation statements)

References 40 publications

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“…+ T E does not occur until ~72 hours after LCMV challenge, but proliferation starts somewhat earlier in the MedLNs (19,21). Enumerating p14 + T E in the MedLNs on day 3 or 4 after infection, we found that their expansions in p14 2e2 -p14 2e5 chimeras tracked exactly with original p14 + T N input numbers, indicating that the early kinetics of p14…”

Section: Evolving Functionalities Of Aging Antiviral Cd8mentioning

confidence: 63%

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Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

Eberlein¹,

Davenport²,

Nguyen³

et al. 2016

Journal of Clinical Investigation

176

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Section: Evolving Functionalities Of Aging Antiviral Cd8mentioning

confidence: 63%

“…+ T E responses already began to diverge in the LNs, especially the draining mediastinal LNs (MedLNs) (21) where enhanced proliferation rates of aged II° p14…”

Section: Kinetics Of Early Ii° Cd8 + T E Expansions In Draining and Nmentioning

confidence: 99%

Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

Eberlein¹,

Davenport²,

Nguyen³

et al. 2016

Journal of Clinical Investigation

176

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“…The increased number of gp100-specific spots in the spleen compared to the dLNs from mice immunized with the CpG-gp-E2 formulation may be a result of the kinetics following a virus-induced immune response, where lymphocytes in the initial dLNs are known to respond earlier than those in the spleen [50]. It is entirely possible that CD8 + T cell expansion peaked in the lymph nodes and started to decline prior to our analyses, as CD8 + T cells may have already exited the lymph nodes or have begun contraction into the memory pool.…”

Section: Resultsmentioning

confidence: 99%

Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses

et al. 2016

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The immune system is a powerful resource for the eradication of cancer, but to overcome the low immunogenicity of tumor cells, a sufficiently strong CD8+ T cell-mediated adaptive immune response is required. Nanoparticulate biomaterials represent a potentially effective delivery system for cancer vaccines, as they can be designed to mimic viruses, which are potent inducers of cellular immunity. We have been exploring the non-viral pyruvate dehydrogenase E2 protein nanoparticle as a biomimetic platform for cancer vaccine delivery. Simultaneous conjugation of a melanoma-associated gp100 epitope and CpG to the E2 nanoparticle (CpG-gp-E2) yielded an antigen-specific increase in the CD8+ T cell proliferation index and IFN-γ secretion by 1.5-fold and 5-fold, respectively, compared to an unbound peptide and CpG formulation. Remarkably, a single nanoparticle immunization resulted in a 120-fold increase in the frequency of melanoma epitope-specific CD8+ T cells in draining lymph nodes and a 30-fold increase in the spleen, relative to free peptide with free CpG. Furthermore, in the very aggressive B16 melanoma murine tumor model, prophylactic immunization with CpG-gp-E2 delayed the onset of tumor growth by approximately 5.5 days and increased animal survival time by approximately 40%, compared to PBS-treated animals. These results show that by combining optimal particle size and simultaneous co-delivery of molecular vaccine components, antigen-specific anti-tumor immune responses can be significantly increased.

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“…Whole lungs were homogenized, and supernatants were subsequently collected and flash-frozen. For plaque assay, supernatants were thawed and plated on BSC40 cells for VACV-infected lungs, MDCK cells for IAVinfected lungs, or Vero cells for either LCMV-or RSV-infected lungs as previously described (10)(11)(12). Briefly, samples were diluted in serum-free medium and plated on the appropriate cell line with rocking for 1 to 1.5 h. For LCMV and RSV, cells were subsequently overlaid with a 1:1 ratio of serum-containing medium and 1% agar.…”

Section: Methodsmentioning

confidence: 99%

The Pulmonary Localization of Virus-Specific T Lymphocytes Is Governed by the Tissue Tropism of Infection

Knudson

Weiss

Hartwig

et al. 2014

J Virol

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The migration of pathogen-specific T cells into nonlymphoid tissues, such as the lung, is critical to control peripheral infections. Use of in vivo intravascular labeling of leukocytes has allowed for improved discrimination between cells located in the blood from cells present within peripheral tissues, such as the lung. This is particularly important in the lung, which is comprised of an intricate network of blood vessels that harbors a large proportion of the total blood volume at any given time. Recent work has demonstrated that >80% of antigen-specific effector CD8 T cells remain in the pulmonary vasculature following an intratracheal infection with a systemic viral pathogen. A n intricate network of blood vessels is associated with the bronchial tree and alveolar sacs of the lung (1). The vascular network is necessary for respiratory function as well as for the trafficking of leukocytes into the lung during infection (2). Leukocytes that remain in the vasculature can be detected by intravenous (i.v.) administration of a specific antibody prior to perfusion and tissue isolation (3-5). Recent work has shown that 80 to 95% of T cell receptor (TCR) transgenic effector and memory CD8 T cells are confined to the pulmonary vasculature following an intratracheal lymphocytic choriomeningitis virus (LCMV) infection despite extensive lung perfusion (4). Importantly, LCMV disseminates systemically even after an intratracheal or intranasal (i.n.) infection. Therefore, it remains unclear what proportion of T cells isolated from a perfused lung are within the lung tissue versus the pulmonary vasculature following an intranasal inoculation with a virus causing a localized respiratory infection.CD8 T cells play a critical role in mediating clearance of acute localized respiratory viral infections such as those caused by respiratory syncytial virus (RSV) and influenza A virus (IAV) (6, 7). Due to the critical role CD8 T cell responses play in mediating the clearance of respiratory viral infections, we sought to determine whether the majority of endogenous virus-specific CD8 T cells were located within lung tissue following a localized pulmonary viral infection. In contrast to systemic infections, our results demonstrate that 80 to 90% of endogenous virus-specific effector and memory CD8 T cells are located within lung tissue following a localized pulmonary viral infection. Furthermore, using cytokine reporter mice, we show that gamma interferon-positive (IFN-␥ ϩ ) endogenous effector CD8 T cells are highly enriched within lung tissue following a respiratory viral infection compared to a systemic infection. These data indicate that the tissue tropism of a virus significantly impacts the localization pattern of virus-specific effector and memory CD8 T cells.

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The Initial Draining Lymph Node Primes the Bulk of the CD8 T Cell Response and Influences Memory T Cell Trafficking after a Systemic Viral Infection

Cited by 34 publications

References 40 publications

Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses

The Pulmonary Localization of Virus-Specific T Lymphocytes Is Governed by the Tissue Tropism of Infection

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