Persistent T Cell Repertoire Perturbation and T Cell Activation in HIV After Long Term Treatment
| Autor: | Evdokia Tsaliki, Gabriele Pollara, Benny Chain, Marc Lipman, James M. Heather, Imran Uddin, Mahdad Noursadeghi, Jennifer K. Roe, Carolin T. Turner, Emily Shaw, Yuxin Sun, James Brown |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Male chronic inflammation Time Factors Anti-HIV Agents T cell T-Lymphocytes Immunology antiretroviral therapy Receptors Antigen T-Cell HIV Infections Biology Lymphocyte Activation HIV Long-Term Survivors Transcriptome 03 medical and health sciences 0302 clinical medicine Immune system blood transcriptome Antigen medicine Cytotoxic T cell Immunology and Allergy Humans 030212 general & internal medicine people living with HIV Original Research human immunodeficiency virus T cell activation Repertoire Gene Expression Profiling T-cell receptor High-Throughput Nucleotide Sequencing Middle Aged 030104 developmental biology medicine.anatomical_structure Cross-Sectional Studies Phenotype Treatment Outcome Case-Control Studies Female lcsh:RC581-607 T cell repertoire Clonal selection |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | ObjectiveIn people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation.MethodsWe conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records.ResultsT cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts. We found no evidence that these expansions were driven by cytomegalovirus or another common antigen. Increased frequency of long CDR3 sequences and reduced frequency of public sequences among the expanded clones implicated abnormal thymic selection as a contributing factor. These abnormalities in the repertoire correlated with systems level evidence of persistent T cell activation in genome-wide blood transcriptomes.ConclusionsThe diversity of T cell receptor repertoires in PLHIV on long term anti-retroviral therapy remains significantly depleted, and skewed by idiosyncratic clones, partly attributable to altered thymic output and associated with T cell mediated chronic immune activation. Further investigation of thymic function and the antigenic drivers of T cell clonal selection in PLHIV are critical to efforts to fully re-establish normal immune function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|