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Involvement of CD8+ T cell subsets in early response to vascular injury in patients with peripheral artery disease in vivo.

ABSTRACT: AIMS:Adaptive immunity is critical in vascular remodelling following arterial injury. We hypothesized that acute changes in T cells at a percutaneous transluminal angioplasty (PTA) site could serve as an index of their potential interaction with the injured vascular wall. METHODS AND RESULTS:T cell subsets were characterised in 45 patients with Rutherford 3-4 peripheral artery disease (PAD) undergoing PTA. Direct angioplasty catheter blood sampling was performed before and immediately after the procedure. PTA was associated with an acute reduction of ?/?-TcR CD8+ T cells. Further characterisation revealed significant reduction in pro-atherosclerotic CD28nullCD57+ T cells, effector (CD45RA+CCR7-) and effector memory (CD45RA-CCR7-) cells, in addition to cells bearing activation (CD69, CD38) and tissue homing/adhesion markers (CD38, CCR5). CONCLUSIONS:The acute reduction observed here is likely due to the adhesion of cells to the injured vascular wall, suggesting that immunosenescent, activated effector CD8+ cells have a role in the early vascular injury immune response following PTA in PAD patients.

SUBMITTER: Maga P

PROVIDER: S-EPMC6281164 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Involvement of CD8+ T cell subsets in early response to vascular injury in patients with peripheral artery disease in vivo.

Maga Pawel P Mikolajczyk Tomasz P TP Partyka Lukasz L Siedlinski Mateusz M Maga Mikolaj M Krzanowski Marek M Malinowski Krzysztof K Luc Kevin K Nizankowski Rafal R Bhatt Deepak L DL Guzik Tomasz J TJ

Clinical immunology (Orlando, Fla.) 20180621

<h4>Aims</h4>Adaptive immunity is critical in vascular remodelling following arterial injury. We hypothesized that acute changes in T cells at a percutaneous transluminal angioplasty (PTA) site could serve as an index of their potential interaction with the injured vascular wall.<h4>Methods and results</h4>T cell subsets were characterised in 45 patients with Rutherford 3-4 peripheral artery disease (PAD) undergoing PTA. Direct angioplasty catheter blood sampling was performed before and immedia ...[more]

PMID: 29936303

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Project description:Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of γδ T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of γδ T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of γδ T cells. Our results demonstrated that the frequencies and absolute numbers of total γδ T cells and Vδ2+ T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of Vδ1+ T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the Vδ1/Vδ2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total γδ T cells, Vδ2+T cells and Vδ2-T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total γδ T cells, Vδ2+T cells, and Vδ2-T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDL-C levels and frequencies of CD3+γδ+ T cells, CD69+Vδ2+T cells, NKG2D+Vδ2+T cells, and NKp46+Vδ2+T cells. By contrast, there was an inverse correlation between the levels of serum LDL-C and the frequencies of CD69+Vδ2-T cells and NKp46+Vδ2-T cells. Accordingly, these findings could help us to better understand the roles of γδ T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting γδ T cells for CAD patients.

Project description:Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets through the use of hybrid monoclonal antibodies (mAbs) to DC surface receptors fused to antigens of interest opened new perspectives for the induction of robust immune responses. Normally, the hybrid mAbs are administered with adjuvants that induce DC maturation. In this work, we targeted an antigen to the CD8?+ or the CD8?- DC subsets in the presence of CpG oligodeoxinucleotides (ODN) or bacterial flagellin, using hybrid ?DEC205 or ?DCIR2 mAbs, respectively. We also accessed the role of toll-like receptors (TLRs) 5 and 9 signaling in the induction of specific humoral and cellular immune responses. Wild-type and TLR5 or TLR9 knockout mice were immunized with two doses of the hybrid ?DEC205 or ?DCIR2 mAbs, as well as with an isotype control, together with CpG ODN 1826 or flagellin. A chimeric antigen containing the Plasmodium vivax 19?kDa portion of the merozoite surface protein (MSP119) linked to the Pan-allelic DR epitope was fused to each mAb. Specific CD4+ T cell proliferation, cytokine, and antibody production were analyzed. We found that CpG ODN 1826 or flagellin were able to induce CD4+ T cell proliferation, CD4+ T cells producing pro-inflammatory cytokines, and specific antibodies when the antigen was targeted to the CD8?+ DC subset. On the other hand, antigen targeting to CD8?- DC subset promoted specific antibody responses and proliferation, but no detectable pro-inflammatory CD4+ T cell responses. Also, specific antibody responses after antigen targeting to CD8?+ or CD8?- DCs were reduced in the absence of TLR9 or TLR5 signaling, while CD4+ T cell proliferation was mainly affected after antigen targeting to CD8?+ DCs and in the absence of TLR9 signaling. These results extend our understanding of the modulation of specific immune responses induced by antigen targeting to DCs in the presence of different adjuvants. Such knowledge may be useful for the optimization of DC-based vaccines.

Dataset Information

Involvement of CD8+ T cell subsets in early response to vascular injury in patients with peripheral artery disease in vivo.

Publications

Involvement of CD8+ T cell subsets in early response to vascular injury in patients with peripheral artery disease in vivo.

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