Related Experiment Videos
MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection:
Dominic Paquin-Proulx1, Benjamin C Greenspun1, Emanuela A S Costa2
1Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, United States of America.
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.
Insights
Human T-lymphotropic virus type 1 (HTLV-1) infection reduces Mucosal-associated invariant T (MAIT) cells, impairing their function. This may increase susceptibility to infections like tuberculosis in HTLV-1 patients.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Human T-lymphotropic virus type 1 (HTLV-1) causes inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
- The reasons for HAM/TSP development in a minority of HTLV-1 infected individuals are unclear.
- HTLV-1 infection is linked to increased susceptibility to Mycobacterium tuberculosis (Mtb) infection, suggesting immune defects.
Purpose of the Study:
- To investigate the frequency, phenotype, and function of Mucosal-associated invariant T (MAIT) cells in HTLV-1 infected individuals.
- To determine if HTLV-1 infection causes perturbations in MAIT cells similar to other chronic viral infections.
- To explore the role of MAIT cells in HTLV-1 pathogenesis and susceptibility to infections.
Main Methods:
- Flow cytometry was used to analyze MAIT cells.
- A cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients was studied.
- MAIT cell frequency, activation markers (CD38, HLA-DR), chemokine receptors (CCR6, CD127), transcription factor (PLZF), and cytokine response (IFNγ) were assessed.
Main Results:
- MAIT cells were reduced in HTLV-1 infected subjects.
- MAIT cells exhibited high co-expression of CD38 and HLA-DR, indicating activation.
- MAIT cells showed poor IFNγ response upon stimulation and reduced PLZF expression in HAM/TSP patients.
Conclusions:
- HTLV-1 infection is associated with reduced frequency and impaired function of MAIT cells.
- MAIT cell perturbations are linked to immune activation, not direct HTLV-1 infection.
- While not directly implicated in HAM/TSP pathogenesis, MAIT cell dysfunction may contribute to increased susceptibility to other infections in HTLV-1 patients.