Age but not disease progression defines CD4 + and CD8 + T stem cell memory levels in human retroviral infections: contrasting effects of HTLV-1 and HIV-1
Year: 2018
Type: preprint
Study design: Observational Study
Abstract: Background Human CD4 + and CD8 + stem cell memory T cells (T SCM ) represent a minor fraction of circulating lymphocytes characterized by stemness and long-term in vivo persistence. CD4 + T SCM are preferentially infected and constitute a reservoir for HIV-1, whereas CD8 + T SCM appear to play a protective role. However, little is known about CD4 + and CD8 + T SCM in the only other human pathogenic retroviral infection, human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is the etiological agent of both Adult T-cell Leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraperesis (HAM/TSP), a neuroinflammatory disorder. In ATL, CD4 + T SCM cells were identified as the hierarchical leukemic stem cell, but data in HAM/TSP are lacking. Age is a major risk factor for both ATL and HAM/TSP, as both diseases generally manifest several decades after infection. Therefore, we explored a possible link between T SCM , age and disease status in human retroviral infections in a cross-sectional study, using multiparametric flow cytometry. Results We found that CD4 + or CD8 + T SCM levels (quantified as CD3 + CD45RA + CD45RO − CD27 + CCR7 + Fas hi ) do not differ between healthy controls and untreated HTLV-1 infected individuals with and without neuroinflammatory disorder. However, we found both T SCM as well as CD8 + T SCM significantly accumulated with age, resulting in a >400% increase in elderly HTLV-1 infected individuals (>60 years). A significant correlation between age and T SCM signature genes was validated at the transcriptome level in an independent cohort. CD8 + but not CD4 + T SCM were significantly decreased in untreated HIV-1 infection. Unexpectedly, CD8 + T SCM recovery upon successful antiretroviral treatment was essentially complete (92.2±11.0%) in younger (<45 years) individuals, but significantly lower (37.3±6.1%) in older (>45 years) individuals (p=0.0003). Conclusion In HTLV-1 infection, an age-dependent accumulation of CD4 + and CD8 + T SCM points towards a possible protective role of CD8 T SCM in the elderly against leukemic but not neuroinflammatory disease. HIV-1-infected individuals lose their ability to restore CD8 + T SCM levels upon successful antiretroviral therapy at later age (>45 years), which might eventually lead to immunological failure and decreased vaccine efficacy.
DOI: 10.1101/473363
Authors: Soraya Maria Menezes, Fabio Eudes Leal, Susan Pereira Ribeiro, Tim Dierckx, Mario Roederer, Devi SenGupta, Douglas F. Nixon, Johan Van Weyenbergh
Institutions: Rega Institute for Medical Research, KU Leuven, Instituto Nacional de Câncer - INCA, Case Western Reserve University, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, University of California, San Francisco, George Washington University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2901068516