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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.


Associations between immune activation and HTLV-1 proviral load.Associations between proviral load and CD4 T cell (A), CD8 T cell (B), and MAIT cell (C) co-expression of CD38 and HLA-DR. Association between proviral load and MAIT cell frequency (D). Association between co-expression of CD38 and HLA-DR (E) and PD-1 expression (F) by MAIT cells and MAIT cell frequency.
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pone.0175345.g003: Associations between immune activation and HTLV-1 proviral load.Associations between proviral load and CD4 T cell (A), CD8 T cell (B), and MAIT cell (C) co-expression of CD38 and HLA-DR. Association between proviral load and MAIT cell frequency (D). Association between co-expression of CD38 and HLA-DR (E) and PD-1 expression (F) by MAIT cells and MAIT cell frequency.

Mentions: We then looked for associations between immune activation and HTLV-1 proviral load. As expected, we found a positive association between HTLV-1 proviral load and CD4 T cell activation (r = 0.5175, p = 0.0232, Fig 3A) but not with CD8 T cell activation (p = 0.9460, Fig 3B) or with MAIT cell activation (p = 0.2551, Fig 3C). HTLV-1 proviral load was also not associated with MAIT cell frequency (p = 0.4999, Fig 3D). However, MAIT cell frequency was inversely associated with their co-expression of CD38 and HLA-DR (p<0.001, Fig 3E) but not with PD-1 expression (p = 0.3306, Fig 3F). This suggests that immune activation associated with HTLV-1 infection results in loss of MAIT cells.


MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications
Associations between immune activation and HTLV-1 proviral load.Associations between proviral load and CD4 T cell (A), CD8 T cell (B), and MAIT cell (C) co-expression of CD38 and HLA-DR. Association between proviral load and MAIT cell frequency (D). Association between co-expression of CD38 and HLA-DR (E) and PD-1 expression (F) by MAIT cells and MAIT cell frequency.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0175345.g003: Associations between immune activation and HTLV-1 proviral load.Associations between proviral load and CD4 T cell (A), CD8 T cell (B), and MAIT cell (C) co-expression of CD38 and HLA-DR. Association between proviral load and MAIT cell frequency (D). Association between co-expression of CD38 and HLA-DR (E) and PD-1 expression (F) by MAIT cells and MAIT cell frequency.
Mentions: We then looked for associations between immune activation and HTLV-1 proviral load. As expected, we found a positive association between HTLV-1 proviral load and CD4 T cell activation (r = 0.5175, p = 0.0232, Fig 3A) but not with CD8 T cell activation (p = 0.9460, Fig 3B) or with MAIT cell activation (p = 0.2551, Fig 3C). HTLV-1 proviral load was also not associated with MAIT cell frequency (p = 0.4999, Fig 3D). However, MAIT cell frequency was inversely associated with their co-expression of CD38 and HLA-DR (p<0.001, Fig 3E) but not with PD-1 expression (p = 0.3306, Fig 3F). This suggests that immune activation associated with HTLV-1 infection results in loss of MAIT cells.

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.