title: MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications.
abstract: HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America.
authors.forename: Dominic
authors.identifier: http://orcid.org/0000-0003-1407-3414
authors.initials: D
authors.lastname: Paquin-Proulx
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Greenspun
authors.affiliation: Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Emanuela A S
authors.initials: EA
authors.lastname: Costa
authors.affiliation: Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Aluisio C
authors.initials: AC
authors.lastname: Segurado
authors.affiliation: Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America.
authors.forename: Fabio E
authors.initials: FE
authors.lastname: Leal
mesh_terms: D000328:Adult; D000368:Aged; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D015490:HTLV-I Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology / Q000473:pathology*; D019562:Viral Load