title: An altered maturation and adhesion phenotype of dendritic cells in diseased individuals compared to asymptomatic carriers of human T cell leukemia virus type 1.
abstract: The immunopathogenic mechanisms underlying human T cell leukemia virus type 1 (HTLV-1)-mediated diseases such as adult T cell leukemia (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are not clearly understood. As critical effectors of antiviral immune response, dendritic cells (DCs) are implicated to play an important role in determining the outcome of HTLV-1 infection. However, a complete understanding of their role in any disease pathogenesis requires extensive assessment of the phenotypic and functional state of DCs. To enable this, we developed a polychromatic antibody cocktail comprising key phenotypic and functional markers of DCs and applied it in a patient cohort from the HTLV-1 endemic region, Jamaica, consisted of seronegative controls, asymptomatic carriers (ACs), ATL, and HAM/TSP patients. This ex vivo analyses included two major subsets of blood DCs, myeloid and plasmacytoid (mDCs and pDCs, respectively). The comparative analyses of results demonstrated a decreased pDC frequency in both ATL and HAM/TSP patients as compared to ACs and seronegative controls. Similarly, CD86 expression on both mDCs and pDCs was significantly higher in HAM/TSP (but not ATL) patients compared to ACs. Interestingly, HLA-DR expression was significantly lower on pDCs of patients as compared to carriers; however, for mDCs, only the HAM/TSP group had significantly lower expression of HLA-DR. Unlike HAM/TSP individuals, ATL individuals had higher HLA-ABC expression on mDCs compared to ACs. Finally, both mDCs and pDCs of HAM/TSP patients had significantly higher expression of the programmed death ligand 1 (PD-L1) compared to ACs. Overall, this study suggests that DCs exhibit a differential phenotypic and functional profile between patients (ATL and HAM/TSP) and carriers of HTLV-1 and could provide an important tool for understanding HTLV-1 immunopathogenesis during infection and disease.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Sharrón L
authors.initials: SL
authors.lastname: Manuel
authors.forename: Mohit
authors.initials: M
authors.lastname: Sehgal
authors.forename: Zafar K
authors.initials: ZK
authors.lastname: Khan
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Pooja
authors.initials: P
authors.lastname: Jain
mesh_terms: D000328:Adult; D000914:Antibodies, Viral; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D002353:Carrier State / Q000821:virology*; D002448:Cell Adhesion / Q000235:genetics*; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000235:genetics* / Q000276:immunology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens