[PMID]: | 28701399 |
[Au] Autor: | Hensel MT; Peng T; Cheng A; De Rosa SC; Wald A; Laing KJ; Jing L; Dong L; Magaret AS; Koelle DM |
[Ad] Endereço: | Department of Global Health, Program in Pathobiology, University of Washington, Seattle, Washington, USA. |
[Ti] Título: | Selective Expression of CCR10 and CXCR3 by Circulating Human Herpes Simplex Virus-Specific CD8 T Cells. |
[So] Source: | J Virol;91(19), 2017 Oct 01. |
[Is] ISSN: | 1098-5514 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Herpes simplex virus (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T cells. CLA/ESL mediates adhesion of T cells to inflamed vascular endothelium. Later stages in T-cell homing involve chemokines (Ch) and lymphocyte chemokine receptors (ChR) for vascular wall arrest and diapedesis. Several candidate ChR have been implicated in skin homing. We measured cell surface ChR on HSV-specific human peripheral blood CD8 T cells and extended our studies to HSV-1. We observed preferential cell surface expression of CCR10 and CXCR3 by HSV-specific CD8 T cells compared to CD8 T cells specific for control viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), and compared to bulk memory CD8 T cells. CXCR3 ligand mRNA levels were selectively increased in skin biopsy specimens from persons with recurrent HSV-2, while the mRNA levels of the CCR10 ligand CCL27 were equivalent in lesion and control skin. Our data are consistent with a model in which CCL27 drives baseline recruitment of HSV-specific CD8 T cells expressing CCR10, while interferon-responsive CXCR3 ligands recruit additional cells in response to virus-driven inflammation. HSV-2 causes very localized recurrent infections in the skin and genital mucosa. Virus-specific CD8 T cells home to the site of recurrent infection and participate in viral clearance. The exit of T cells from the blood involves the use of chemokine receptors on the T-cell surface and chemokines that are present in infected tissue. In this study, circulating HSV-2-specific CD8 T cells were identified using specific fluorescent tetramer reagents, and their expression of several candidate skin-homing-associated chemokine receptors was measured using flow cytometry. We found that two chemokine receptors, CXCR3 and CCR10, are upregulated on HSV-specific CD8 T cells in blood. The chemokines corresponding to these receptors are also expressed in infected tissues. Vaccine strategies to prime CD8 T cells to home to HSV lesions should elicit these chemokine receptors if possible to increase the homing of vaccine-primed cells to sites of infection. |
[Mh] Termos MeSH primário: |
Linfócitos T CD8-Positivos/imunologia Quimiocina CCL27/imunologia Herpes Simples/imunologia Herpesvirus Humano 2/imunologia Ativação Linfocitária/imunologia Receptores CCR10/imunologia Receptores CXCR3/imunologia
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[Mh] Termos MeSH secundário: |
Antígenos de Diferenciação de Linfócitos T/imunologia Linfócitos T CD8-Positivos/metabolismo Quimiocina CCL27/genética Citomegalovirus/imunologia Feminino Citometria de Fluxo Herpes Simples/virologia Herpesvirus Humano 4/imunologia Seres Humanos Memória Imunológica/imunologia Masculino Glicoproteínas de Membrana/imunologia RNA Mensageiro/genética Receptores CCR10/biossíntese Receptores CCR10/genética Receptores CXCR3/biossíntese Receptores CXCR3/genética Pele/virologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antigens, Differentiation, T-Lymphocyte); 0 (CCL27 protein, human); 0 (CCR10 protein, human); 0 (CTAGE1 protein, human); 0 (CXCR3 protein, human); 0 (Chemokine CCL27); 0 (Membrane Glycoproteins); 0 (RNA, Messenger); 0 (Receptors, CCR10); 0 (Receptors, CXCR3) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 170926 |
[Lr] Data última revisão:
| 170926 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170714 |
[St] Status: | MEDLINE |
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