Direct Visualization of Antigen-specific CD8+T Cells during the Primary Immune Response to Epstein-Barr Virus In Vivo

Callan, Margaret; Tan, Linda; Annels, NE; Ogg, Graham S.; Wilson, Jamie; O’Callaghan, Christopher A.; Steven, Neil; McMichael, Andrew J.; Rickinson, A. B.

doi:10.1084/jem.187.9.1395

Cited by 822 publications

(576 citation statements)

References 25 publications

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“…In persistent simian immunodeficiency virus infection in macaques, Kuroda et al 26 showed that epitope-specific T cells can account for as much as 10% of CD8 + T cells in the blood. Callan et al 27 have shown that between 7 and 44% of blood CD8 + T cells are EBV-specific in acute infection and the total number of CD8 + T cells is greatly increased, almost entirely by antigen-specific cells. MHC-II based tetramers were also prepared and widely used for the staining of CD4 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity

Yang

Tao

et al. 2000

Gene Ther

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Section: Discussionmentioning

confidence: 99%

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity

Yang

Tao

et al. 2000

Gene Ther

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“…These data suggested that only a minority of circulating melan-A-specific CTL in a minority of melanoma patients had a history of Ag exposure. However, CD45 isoforms are not in themselves adequate markers of memory/naivety, since memory cells can change expression patterns in vitro (18,19), and subpopulations of memory CTL specific for viral Ags can express converse CD45 isoforms in vivo (20,21).…”

mentioning

confidence: 99%

A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response

Dunbar¹,

Smith²,

Chao

et al. 2000

The Journal of Immunology

123

117

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In a significant proportion of melanoma patients, CTL specific for the melan-A26/7–35 epitope can be detected in peripheral blood using HLA-A2/peptide tetramers. However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer+ cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer+ cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7+ CD45R0− CD45RA+ phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer+ cells were shifted toward a CCR7− CD45R0+ CD45RA− phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.

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“…Following and monitoring spontaneous and postvaccinal immune responses remain elusive and limited to a handful of systems where TCRtransgenic mice are available. This paradigm has marginally benefited from the development of MHC tetramers that has been so successful for the detection of Ag-specific CD8 ϩ cytotoxic T cells (3,4). The reasons for the discrepancy between MHC class I and MHC class II tetramers are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The multimerization of MHC-peptide complexes answers partially this latter limitation by allowing an avidity effect and the staining of Ag-specific T cells (1,2). However, this method, largely used for the detection of cytotoxic CD8 ϩ T cells (3,4), has limitations. The first one of them is simply the geometry of display.…”

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confidence: 99%

“…As a step in this direction, we have developed liposomes that display recombinant MHC class II molecules and can bind in an Ag-specific manner CD4 ϩ T cells that cannot be detected using tetramers. These artificial APC (AAPC) 3 were tested and used in the context of the anti-OVA CD4 ϩ T cell response, one of the most studied antigenic systems in the mouse. AAPC displaying I-A b -OVA 323-339 molecules were used to detect specific hybridoma T cells, naive T cells, and primary T cells responding to an antigenic challenge.…”

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confidence: 99%

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Detection of Low-Avidity CD4+ T Cells Using Recombinant Artificial APC: Following the Antiovalbumin Immune Response

Mallet-Designe¹,

Stratmann²,

Homann

et al. 2003

The Journal of Immunology

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Subtle differences oppose CD4+ to CD8+ T cell physiologies that lead to different arrays of effector functions. Interestingly, this dichotomy has also unexpected practical consequences such as the inefficacy of many MHC class II tetramers in detecting specific CD4+ T cells. As a mean to study the CD4+ anti-OVA response in H-2d and H-2b genetic backgrounds, we developed I-Ad- and I-Ab-OVA recombinant MHC monomers and tetramers. We were able to show that in this particular system, despite normal biological activity, MHC class II tetramers failed to stain specific T cells. This failure was shown to be associated with a lack of cooperation between binding sites within the tetramer as measured by surface plasmon resonance. This limited cooperativeness translated into a low “functional avidity” and very transient binding of the tetramers to T cells. To overcome this biophysical barrier, recombinant artificial APC that display MHC molecules in a lipid bilayer were developed. The plasticity and size of the MHC-bearing fluorescent liposomes allowed binding to Ag-specific T cells and the detection of low numbers of anti-OVA T cells following immunization. The same liposomes were able, at 37°C, to induce the full reorganization of the T cell signaling molecules and the formation of an immunological synapse. Artificial APC will allow T cell detection and the dissection of the molecular events of T cell activation and will help us understand the fundamental differences between CD4+ and CD8+ T cells.

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Direct Visualization of Antigen-specific CD8+T Cells during the Primary Immune Response to Epstein-Barr Virus In Vivo

Cited by 822 publications

References 25 publications

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity

A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response

Detection of Low-Avidity CD4+ T Cells Using Recombinant Artificial APC: Following the Antiovalbumin Immune Response

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