PD-1, a central negative regulatory molecule was one of the early studied mediators of immune exhaustion in chronic infectious diseases, particularly HIV-1 infection [ 6 , 7 ] and in animal viral chronic infectious models [ 12 ]. Please review our privacy policy. Of note, we could not confirm the specific expression of CDTM at the protein level due to the lack of specific antibodies capable of distinguishing between the two isoforms note that CDGPI antibodies poorly recognize the CDTM isoform [ 18 ]. This apparent up-regulation of CD on resting cells and the contribution of ex vivo culture conditions such as the use of human serum require more investigation. All authors were employees of Boehringer Ingelheim Canada when this work was performed. Ivan A D Lessard, Email:

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Samples from the HLA-B27 subject displayed the highest response values.

CD160 isoforms and regulation of CD4 and CD8 T-cell responses

Therapeutic immunopotentiation through the specific targeting of negative and positive immune regulators on T-cells represents an interesting approach to complement current treatment regimens in HIV infection. All authors were employees of Boehringer Ingelheim Canada when this work was performed. Charles Pellerin Mgc-430 Ingelheim Ltd.

This finding shows that functional T-cells may lose their capacity to mibton and suggest that chronicity of infection and viral load levels may be used as predictive markers to identify patients who may benefit from immunotherapeutic intervention that target immune checkpoint molecules.

MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment.


B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. All authors read and approved the final manuscript. Serial dilutions of cellular or codon-optimized CDTM RNA were used to generate a standard for gene-specific expression analysis and to determine changes in transcript levels.

Footnotes Charles Pellerin and Louise Pilote contributed equally to this work. P values were determined by two-tailed paired t test data from three independent healthy donors.

B A representative Loading control for activator beads set 4: Jurkat-CD positive clones were selected with Geneticin as described above. The up-regulation of CD on resting cells ex vivo and its down-regulation following TCR stimulation thus contrasted observations by Cai et al. Matched isotype control antibody for each individual antibody candidate was also used in the assay empty circles and squares. ME designed the study, performed the experiments, analyzed the data and wrote the manuscript.

Funding This work was supported by Boehringer Jinton Canada.

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Identical results were also obtained with anti-CD clone data not shown. Assign software was used to interpret sequence information for allele typing Conexio Genetics, Perth, Australia. Charles Pellerin and Louise Pilote contributed equally to this work. To ensure similar levels of ectopic expression of the individual isoforms in the respective cell lines and to also confirm the absence of intrinsic CD expression, we quantified the CDGPI and CDTM mRNA transcripts ectopically expressed in each of these cell lines.

As shown in Additional file 2the breadth of ex vivo responses was higher in samples from the viremic subjects compared to samples from the successfully treated one.


This article has been cited by other articles in PMC. Michael G Cordingley, Email: Consequently, the interpretation of results based exclusively on HVEM-directed blockade may benefit from additional exploration involving the interacting ligand s. Received May 6; Accepted Jul The presence of these two isoforms of CD and their potential differential expression in T-cells requires further studies, particularly in the context of immune exhaustion.

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Viral immune evasion due to persistence of activated T cells without effector function. However, in some instances such as persistent antigenic stimulation during chronic HIV or other viral infections, these negative regulators accumulate progressively on the cell surface of total and Ag-specific T and B cells [ 5 – 9 ].

Boehringer Ingelheim Canada Ltd. HIV pentamers from each subject is annotated above kgc-340 bar right panel.

We would like also to thank Kishanda Vyboh for careful reading of the manuscript. Indeed, our results showed that HVEM antibodies function differently in ex mjnton T-cell assays on samples isolated from HIV-infected subjects with higher viral loads compared to aviremic subjects. Our functional analyses suggest that a pharmacologic effect in HIV viremic subjects may be elicited through the co-targeting of both CD through Ab-mediated activation and PD-1 through Ab-mediated blockade.