Cutting Edge: In Situ Tetramer Staining of Antigen-Specific T Cells in Tissues

Skinner, Pamela J.; Daniëls, Mark A.; Schmidt, Clint S.; Jameson, Stephen C.; Haase, Ashley T.

doi:10.4049/jimmunol.165.2.613

Cited by 134 publications

(112 citation statements)

References 22 publications

(21 reference statements)

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“…Until recently, tetramers have been limited to ex vivo studies but they can be used to visualize antigen-specific CD8 + T cells in tissue with their spatial relationship to other intact cells in socalled in situ tetramer (IST) staining [58][59][60]. Fresh unfixed tissue is ideally used to allow for flexibility in the TCR for binding to the tetramer.…”

Section: In Situ Tetramer Stainingmentioning

confidence: 99%

See 1 more Smart Citation

MHC–peptide tetramers for the analysis of antigen-specific T cells

Sims

Willberg

Klenerman

2010

Expert Review of Vaccines

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Section: In Situ Tetramer Stainingmentioning

confidence: 99%

“…Vaccines 9(7), (2010) method has only been used successfully by a few groups, and this has mainly been in murine models [58], although some human studies have been performed [60].…”

Section: Reviewmentioning

confidence: 99%

MHC–peptide tetramers for the analysis of antigen-specific T cells

Sims

Willberg

Klenerman

2010

Expert Review of Vaccines

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“…When the analysis was conducted on pooled mucosal biopsies, mononuclear cells (MNC) were isolated by collagenase digestion followed by Ficoll-Hypaque density gradient centrifugation. PBMC and MNC were stained with anti-human CD3 Abs (FITC-labeled; BD PharMingen), anti-human CD8␣␤ Ab (PerCP-labeled; Beckman Coulter), and a PE-labeled Mamu-A*01-Gag p11c conjugate (a gift from J. Altman (Emory University, Atlanta, GA)) (50,51). The samples were analyzed by three-color flow cytometry on a Beckman Cytomics FC500, and the data are presented as percentage of tetramer-positive cells of all CD3 ϩ CD8 ϩ cells.…”

Section: Detection Of Gag P11c-tetramer-staining Cd3 ϩ Cd8 ϩ T Lymphomentioning

confidence: 99%

Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates

Bertley

Kozlowski

Wang

et al. 2004

The Journal of Immunology

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A successful HIV vaccine may need to stimulate antiviral immunity in mucosal and systemic immune compartments, because HIV transmission occurs predominantly at mucosal sites. We report here the results of a combined DNA-modified vaccinia virus Ankara (MVA) vaccine approach that stimulated simian/human immunodeficiency virus (SHIV)-specific immune responses by vaccination at the nasal mucosa. Fifteen male rhesus macaques, divided into three groups, received three nasal vaccinations on day 1, wk 9, and wk 25 with a SHIV DNA plasmid producing noninfectious viral particles (group 1), or SHIV DNA plus IL-2/Ig DNA (group 2), or SHIV DNA plus IL-12 DNA (group 3). On wk 33, all macaques were boosted with rMVA expressing SIV Gag-Pol and HIV Env 89.6P, administered nasally. Humoral responses were evaluated by measuring SHIV-specific IgG and neutralizing Abs in plasma, and SHIV-specific IgA in rectal secretions. Cellular responses were monitored by evaluating blood-derived virus-specific IFN-γ-secreting cells and TNF-α-expressing CD8+ T cells, and blood- and rectally derived p11C tetramer-positive T cells. Many of the vaccinated animals developed both mucosal and systemic humoral and cell-mediated anti-SHIV immune responses, although the responses were not homogenous among animals in the different groups. After rectal challenge of vaccinated and naive animals with SHIV89.6P, all animals became infected. However a subset, including all group 2 animals, were protected from CD4+ T cell loss and AIDS development. Taken together, these data indicate that nasal vaccination with SHIV-DNA plus IL-2/Ig DNA and rMVA can provide significant protection from disease progression.

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“…2,3 The in situ tetramer technique can be used to directly visualize virus-specific CD8 T cells in infected tissues, to determine their spatial relationship with parenchymal target cells, and to examine their local functional activity by comparison with other inflammatory cells. [17][18][19] Using this technique, we describe here a population of intrahepatic HCV-specific interleukin (IL)-10-positive CD8 T cells, the presence of which is associated with protection from severe necroinflammatory liver disease during chronic HCV infection. These data suggest that immunotherapy based on virus-specific regulatory CD8 T cells might be beneficial to limit liver damage.…”

mentioning

confidence: 99%

Intrahepatic virus-specific IL-10-producing CD8 T cells prevent liver damage during chronic hepatitis C virus infection

et al. 2006

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CD8 T cell killing of hepatitis C virus (HCV)-infected hepatocytes is thought to contribute to liver damage during chronic HCV infection, whereas the participation of HCV-nonspecific immune cells is unclear. To visualize the spatial relationship of HCV-specific CD8 T cells with parenchymal target cells, and to examine their local functional activity in relation to hepatocellular necrosis and fibrosis, we used HLA tetramers and confocal microscopy in biopsies from 23 HLA-A2 or HLA-B7 patients with chronic HCV infection. Intrahepatic tetramer؉ (HCV-specific) CD8 T cells protected from hepatic necroinflammatory disease activity, independently of age, gender, viral load, and viral genotype. Indeed, tetramer؉ cells were scattered in the liver within regions of weak fibrosis (low laminin expression) and low hepatocellular apoptosis (TUNEL method), and expressed IL-10 but not IFN␥. By contrast, tetramer-negative CD8 T cells were associated with active necroinflammatory liver disease, colocalized with strong laminin expression and hepatocellular apoptosis, and expressed more frequently IFN␥ than IL-10. Overall, liver regions harboring HCV-specific CD8 T cells tended to be healthier than areas containing only inflammatory cells of undefined specificity. In conclusion, HCV-specific IL-10-producing CD8 T cells, although not cytotoxic and unable to control viral replication, can attenuate hepatocellular necrosis, liver fibrosis, and inflammation mediated by bystander T cells, and may thus represent antigen-induced regulatory CD8 T cells. Therapeutic modulation of the intrahepatic balance between specific and bystander CD8 T cells might be beneficial in patients with chronic hepatitis C. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/ index.html).

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Cutting Edge: In Situ Tetramer Staining of Antigen-Specific T Cells in Tissues

Cited by 134 publications

References 22 publications

MHC–peptide tetramers for the analysis of antigen-specific T cells

MHC–peptide tetramers for the analysis of antigen-specific T cells

Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates

Intrahepatic virus-specific IL-10-producing CD8 T cells prevent liver damage during chronic hepatitis C virus infection

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