Limits...
MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

View Article: PubMed Central - PubMed

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.

No MeSH data available.


MAIT cells are functionally impaired in HTLV-1 infection.PBMCs were stimulated with E. coli for 24h at a MOI of 10 and Monensin was added during the last 6 hours before staining for surface antigens and intracellular staining for IFNγ. Representative flow plots of CD69 expression and IFNγ production by MAIT cells (CD3+ Vα7.2+ CD161+) from healthy controls and HTLV-1-infected individuals (A). Production of IFNγ by MAIT cells in healthy controls (n = 11) and HTLV-1-infected subjects (n = 17) (B). Production of IFNγ by MAIT cells in asymptomatic (n = 8), and HAM/TSP (n = 9) HTLV-1-infected subjects (C). CD69 expression by MAIT cells in healthy controls and HTLV-1-infected subjects (D). CD69 expression by MAIT cells in asymptomatic, and HAM/TSP HTLV-1-infected subjects (E). * indicates p ≤ 0.05 and ** indicates p < 0.01. The lines and whiskers represent the median and interquartile range respectively.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5383303&req=5

pone.0175345.g006: MAIT cells are functionally impaired in HTLV-1 infection.PBMCs were stimulated with E. coli for 24h at a MOI of 10 and Monensin was added during the last 6 hours before staining for surface antigens and intracellular staining for IFNγ. Representative flow plots of CD69 expression and IFNγ production by MAIT cells (CD3+ Vα7.2+ CD161+) from healthy controls and HTLV-1-infected individuals (A). Production of IFNγ by MAIT cells in healthy controls (n = 11) and HTLV-1-infected subjects (n = 17) (B). Production of IFNγ by MAIT cells in asymptomatic (n = 8), and HAM/TSP (n = 9) HTLV-1-infected subjects (C). CD69 expression by MAIT cells in healthy controls and HTLV-1-infected subjects (D). CD69 expression by MAIT cells in asymptomatic, and HAM/TSP HTLV-1-infected subjects (E). * indicates p ≤ 0.05 and ** indicates p < 0.01. The lines and whiskers represent the median and interquartile range respectively.

Mentions: Finally, we stimulated PBMCs from healthy controls and HTLV-1-infected subjects with fixed E. coli to stimulate MAIT cells and evaluated their production of IFNγ and up-regulation of CD69 (Fig 6A). There was no difference in spontaneous IFNγ production by MAIT cells in unstimulated samples between the groups (S4 Fig). IFNγ production following E. coli stimulation was lower in HTLV-1-infected individuals compared to healthy controls (Fig 6B), and there was no difference between asymptomatic carriers and HAM/TSP patients (Fig 6C). We observed a non-significant trend for a reduction in CD69 up-regulation in the HTLV-1-infected subjects compared to controls and no difference between asymptomatic carriers and HAM/TSP patients (Fig 6D and 6E). Our results show that HTLV-1 infection is associated with a poor MAIT cell IFNγ response following bacterial stimulation.


MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications
MAIT cells are functionally impaired in HTLV-1 infection.PBMCs were stimulated with E. coli for 24h at a MOI of 10 and Monensin was added during the last 6 hours before staining for surface antigens and intracellular staining for IFNγ. Representative flow plots of CD69 expression and IFNγ production by MAIT cells (CD3+ Vα7.2+ CD161+) from healthy controls and HTLV-1-infected individuals (A). Production of IFNγ by MAIT cells in healthy controls (n = 11) and HTLV-1-infected subjects (n = 17) (B). Production of IFNγ by MAIT cells in asymptomatic (n = 8), and HAM/TSP (n = 9) HTLV-1-infected subjects (C). CD69 expression by MAIT cells in healthy controls and HTLV-1-infected subjects (D). CD69 expression by MAIT cells in asymptomatic, and HAM/TSP HTLV-1-infected subjects (E). * indicates p ≤ 0.05 and ** indicates p < 0.01. The lines and whiskers represent the median and interquartile range respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383303&req=5

pone.0175345.g006: MAIT cells are functionally impaired in HTLV-1 infection.PBMCs were stimulated with E. coli for 24h at a MOI of 10 and Monensin was added during the last 6 hours before staining for surface antigens and intracellular staining for IFNγ. Representative flow plots of CD69 expression and IFNγ production by MAIT cells (CD3+ Vα7.2+ CD161+) from healthy controls and HTLV-1-infected individuals (A). Production of IFNγ by MAIT cells in healthy controls (n = 11) and HTLV-1-infected subjects (n = 17) (B). Production of IFNγ by MAIT cells in asymptomatic (n = 8), and HAM/TSP (n = 9) HTLV-1-infected subjects (C). CD69 expression by MAIT cells in healthy controls and HTLV-1-infected subjects (D). CD69 expression by MAIT cells in asymptomatic, and HAM/TSP HTLV-1-infected subjects (E). * indicates p ≤ 0.05 and ** indicates p < 0.01. The lines and whiskers represent the median and interquartile range respectively.
Mentions: Finally, we stimulated PBMCs from healthy controls and HTLV-1-infected subjects with fixed E. coli to stimulate MAIT cells and evaluated their production of IFNγ and up-regulation of CD69 (Fig 6A). There was no difference in spontaneous IFNγ production by MAIT cells in unstimulated samples between the groups (S4 Fig). IFNγ production following E. coli stimulation was lower in HTLV-1-infected individuals compared to healthy controls (Fig 6B), and there was no difference between asymptomatic carriers and HAM/TSP patients (Fig 6C). We observed a non-significant trend for a reduction in CD69 up-regulation in the HTLV-1-infected subjects compared to controls and no difference between asymptomatic carriers and HAM/TSP patients (Fig 6D and 6E). Our results show that HTLV-1 infection is associated with a poor MAIT cell IFNγ response following bacterial stimulation.

View Article: PubMed Central - PubMed

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 IFN&gamma; 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.

No MeSH data available.