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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

Expression levels of different markers by CD161++CD8+ T-cell subsets in the study population.(A) Zebra plots of double-gating strategy (gated on the CD161++ CD8+ T cells) show staining with 4 different markers (CD103, PD-1, CCR6, CCR5) on representative samples from a HC and a CPTN. HCs showed increased amount of CCR6-expressing MAIT cells and decreased amount of PD-1 expressing MAIT cells compared to CPTNs. (B) HC showed significantly lower expression level of inhibitory receptor, PD-1 while HIV/TB co-infected patients show significantly increased PD-1 expressing MAIT cells. (C) Significantly increased CCR6-expressing MAIT cells were found in HCs compared to HIV and TB infected groups. (D) No significant difference was observed in CCR5 expression levels by MAIT cells among the different study subjects. The significant difference in CCR5 expression between HVTPs and HCs may be due to the limited number of samples. All graphs show median (red bars) and range (blue whiskers); P values are reported for two-sided Mann-Whitney tests with threshold for significance P = 0.025 after Bonferroni correction for 2 comparisons. (Note: TN, treatment naïve; TP, treatment positive; HC, healthy control; CP, HIV/TB co-infection; HV, HIV mono-infection).
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pone.0124659.g003: Expression levels of different markers by CD161++CD8+ T-cell subsets in the study population.(A) Zebra plots of double-gating strategy (gated on the CD161++ CD8+ T cells) show staining with 4 different markers (CD103, PD-1, CCR6, CCR5) on representative samples from a HC and a CPTN. HCs showed increased amount of CCR6-expressing MAIT cells and decreased amount of PD-1 expressing MAIT cells compared to CPTNs. (B) HC showed significantly lower expression level of inhibitory receptor, PD-1 while HIV/TB co-infected patients show significantly increased PD-1 expressing MAIT cells. (C) Significantly increased CCR6-expressing MAIT cells were found in HCs compared to HIV and TB infected groups. (D) No significant difference was observed in CCR5 expression levels by MAIT cells among the different study subjects. The significant difference in CCR5 expression between HVTPs and HCs may be due to the limited number of samples. All graphs show median (red bars) and range (blue whiskers); P values are reported for two-sided Mann-Whitney tests with threshold for significance P = 0.025 after Bonferroni correction for 2 comparisons. (Note: TN, treatment naïve; TP, treatment positive; HC, healthy control; CP, HIV/TB co-infection; HV, HIV mono-infection).

Mentions: We further investigated the expression levels of PD-1 inhibitory receptor on the CD161++/MAIT cell populations in HIV mono- and HIV/TB co-infected patients. Our result showed that PD-1 expression was significantly increased on CD161++ MAIT cells of treatment naïve HIV/TB co-infected patients (median, 12.1%; range 0–33.3; P<0.001), treatment naïve HIV-infected patients (median, 3.2%; range, 0–27.8; P<0.05), and HIV-infected patients under treatment (median, 3.5%; range 0–12.8; P<0.05) as compared to HCs (median, 1.14%; range, 0–3.85) (Fig 3A and 3B).


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)

Expression levels of different markers by CD161++CD8+ T-cell subsets in the study population.(A) Zebra plots of double-gating strategy (gated on the CD161++ CD8+ T cells) show staining with 4 different markers (CD103, PD-1, CCR6, CCR5) on representative samples from a HC and a CPTN. HCs showed increased amount of CCR6-expressing MAIT cells and decreased amount of PD-1 expressing MAIT cells compared to CPTNs. (B) HC showed significantly lower expression level of inhibitory receptor, PD-1 while HIV/TB co-infected patients show significantly increased PD-1 expressing MAIT cells. (C) Significantly increased CCR6-expressing MAIT cells were found in HCs compared to HIV and TB infected groups. (D) No significant difference was observed in CCR5 expression levels by MAIT cells among the different study subjects. The significant difference in CCR5 expression between HVTPs and HCs may be due to the limited number of samples. All graphs show median (red bars) and range (blue whiskers); P values are reported for two-sided Mann-Whitney tests with threshold for significance P = 0.025 after Bonferroni correction for 2 comparisons. (Note: TN, treatment naïve; TP, treatment positive; HC, healthy control; CP, HIV/TB co-infection; HV, HIV mono-infection).
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pone.0124659.g003: Expression levels of different markers by CD161++CD8+ T-cell subsets in the study population.(A) Zebra plots of double-gating strategy (gated on the CD161++ CD8+ T cells) show staining with 4 different markers (CD103, PD-1, CCR6, CCR5) on representative samples from a HC and a CPTN. HCs showed increased amount of CCR6-expressing MAIT cells and decreased amount of PD-1 expressing MAIT cells compared to CPTNs. (B) HC showed significantly lower expression level of inhibitory receptor, PD-1 while HIV/TB co-infected patients show significantly increased PD-1 expressing MAIT cells. (C) Significantly increased CCR6-expressing MAIT cells were found in HCs compared to HIV and TB infected groups. (D) No significant difference was observed in CCR5 expression levels by MAIT cells among the different study subjects. The significant difference in CCR5 expression between HVTPs and HCs may be due to the limited number of samples. All graphs show median (red bars) and range (blue whiskers); P values are reported for two-sided Mann-Whitney tests with threshold for significance P = 0.025 after Bonferroni correction for 2 comparisons. (Note: TN, treatment naïve; TP, treatment positive; HC, healthy control; CP, HIV/TB co-infection; HV, HIV mono-infection).
Mentions: We further investigated the expression levels of PD-1 inhibitory receptor on the CD161++/MAIT cell populations in HIV mono- and HIV/TB co-infected patients. Our result showed that PD-1 expression was significantly increased on CD161++ MAIT cells of treatment naïve HIV/TB co-infected patients (median, 12.1%; range 0–33.3; P<0.001), treatment naïve HIV-infected patients (median, 3.2%; range, 0–27.8; P<0.05), and HIV-infected patients under treatment (median, 3.5%; range 0–12.8; P<0.05) as compared to HCs (median, 1.14%; range, 0–3.85) (Fig 3A and 3B).

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