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Attrition of TCR Vα7.2+ CD161++ MAIT cells in HIV-tuberculosis co-infection is associated with elevated levels of PD-1 expression.

Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK, Ponnampalavanar S, Barathan M, Rukumani DV, Ansari AW, Velu V, Kamarulzaman A, Larsson M, Shankar EM - PLoS ONE (2015)

Bottom Line: Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients.The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT.Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

View Article: PubMed Central - PubMed

Affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia; Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.

ABSTRACT
Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

No MeSH data available.


Related in: MedlinePlus

Correlation analysis between PD-1 expression and CD161++/MAIT cell frequency in the study participants.The MAIT cells frequency correlated inversely with PD-1 expression on MAIT cells (P = 0.0039 and r = -0.4006). Correlation analysis between CD161++/MAIT cell frequencies and PD-1 expression was performed using the Spearman's rank correlation coefficient.
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pone.0124659.g005: Correlation analysis between PD-1 expression and CD161++/MAIT cell frequency in the study participants.The MAIT cells frequency correlated inversely with PD-1 expression on MAIT cells (P = 0.0039 and r = -0.4006). Correlation analysis between CD161++/MAIT cell frequencies and PD-1 expression was performed using the Spearman's rank correlation coefficient.

Mentions: Next, we investigated if the expression of PD-1 on CD161++/MAIT cells had any association with the frequency of these cells in the peripheral circulation of all the study groups. Our results showed that turn-over rates of MAIT cells correlated inversely with surface PD-1 expression on CD161++/MAIT cells (P = 0.0039 and r = -0.4006) (Fig 5). This shows that PD-1 expression levels on MAIT cells likely impacts the frequency of these cells in the peripheral blood. To conclude, we hypothesized that the frequency of CD161++/MAIT cells correlated negatively with surface PD-1 expression on these cells.


Attrition of TCR Vα7.2+ CD161++ MAIT cells in HIV-tuberculosis co-infection is associated with elevated levels of PD-1 expression.

Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK, Ponnampalavanar S, Barathan M, Rukumani DV, Ansari AW, Velu V, Kamarulzaman A, Larsson M, Shankar EM - PLoS ONE (2015)

Correlation analysis between PD-1 expression and CD161++/MAIT cell frequency in the study participants.The MAIT cells frequency correlated inversely with PD-1 expression on MAIT cells (P = 0.0039 and r = -0.4006). Correlation analysis between CD161++/MAIT cell frequencies and PD-1 expression was performed using the Spearman's rank correlation coefficient.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403924&req=5

pone.0124659.g005: Correlation analysis between PD-1 expression and CD161++/MAIT cell frequency in the study participants.The MAIT cells frequency correlated inversely with PD-1 expression on MAIT cells (P = 0.0039 and r = -0.4006). Correlation analysis between CD161++/MAIT cell frequencies and PD-1 expression was performed using the Spearman's rank correlation coefficient.
Mentions: Next, we investigated if the expression of PD-1 on CD161++/MAIT cells had any association with the frequency of these cells in the peripheral circulation of all the study groups. Our results showed that turn-over rates of MAIT cells correlated inversely with surface PD-1 expression on CD161++/MAIT cells (P = 0.0039 and r = -0.4006) (Fig 5). This shows that PD-1 expression levels on MAIT cells likely impacts the frequency of these cells in the peripheral blood. To conclude, we hypothesized that the frequency of CD161++/MAIT cells correlated negatively with surface PD-1 expression on these cells.

Bottom Line: Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients.The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT.Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

View Article: PubMed Central - PubMed

Affiliation: Tropical Infectious Diseases Research and Education Center (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia; Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.

ABSTRACT
Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

No MeSH data available.


Related in: MedlinePlus