The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype
| Autor: | David A. Cooper, Susanna Ip, C Mee Ling Munier, Nathan P. Croft, David C. Tscharke, Gareth Denyer, Warren Kaplan, Michelle Bailey, Sheilajen Alcantara, Stephen J. Kent, Yin Xu, Kazuo Suzuki, Anthony W. Purcell, John Zaunders, Anthony D. Kelleher, David van Bockel, Sue M. Liu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Cytotoxicity Immunologic HIV Infections Vaccinia virus CD8-Positive T-Lymphocytes Lymphocyte Activation Virus Granzymes 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytotoxic T cell Humans Granulysin General Veterinary General Immunology and Microbiology biology Perforin Public Health Environmental and Occupational Health Viral Vaccines Virology ADP-ribosyl Cyclase 1 Up-Regulation CTL 030104 developmental biology Infectious Diseases Phenotype chemistry Granzyme Tissue Array Analysis Immunology biology.protein Molecular Medicine Cytokines Leukocyte Common Antigens Granzyme K Vaccinia 030215 immunology T-Lymphocytes Cytotoxic |
| Zdroj: | Vaccine. 34(44) |
| ISSN: | 1873-2518 |
| Popis: | Background Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. Methods We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. Results A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. Conclusions We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV. |
| Databáze: | OpenAIRE |
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