Limits...
CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

Eberhard JM, Hartjen P, Kummer S, Schmidt RE, Bockhorn M, Lehmann C, Balagopal A, Hauber J, van Lunzen J, Schulze zur Wiesch J - PLoS ONE (2014)

Bottom Line: Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163.CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment.In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6.

View Article: PubMed Central - PubMed

Affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.

ABSTRACT
Mucosal-associated invariant T (MAIT) cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR) Vα7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161(+) MAIT and CD161-TCRVα7.2(+) T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after in vitro stimulation with different cytokines and/or fixed E.coli. Reduced numbers of CD161(+) MAIT cells during HIV infection were detectable in the blood and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment. The loss of CD161(+) MAIT cells was correlated with higher levels of MAIT cell activation; an increased frequency of the CD161-TCRVα7.2(+)T cell subset in HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the irreversible reduction of the CD161(+) MAIT cell subset seems to be an early event in HIV infection that is independent of later stages of the disease. This loss appears to be at least partially due to the distinctive vulnerability of MAIT cells to the pronounced stimulation by microbial products and cytokines during HIV-infection.

Show MeSH

Related in: MedlinePlus

Frequencies of activated CD161+ and CD161– TCR Vα7.2+ cells are elevated in the blood of highly viremic HIV patients.A) Plasma levels of sCD163, sCD14 and IL-18 were measured by ELISA in mostly corresponding samples of healthy controls (HC n = 13), highly viremic HIV-infected patients (high VL n = 18), patients receiving ART (ART n = 17), elite controllers (EC n = 6) and long-term nonprogressors (LTNP n = 6). B) Activated cells were defined as CD38+ and HLA-DR+ double positive cells and their frequency was assessed within the CD4–, MAIT and CD161–TCRVα7.2+ populations. PBMC samples were derived from healthy controls (HC), highly viremic HIV-infected patients (high VL), patients receiving ART (ART), elite controllers (EC) and long-term nonprogressors (LTNP). Groups were compared by Kruskal-Wallis test followed by Dunn's multiple comparison test. P-values smaller than 0.05 were considered significant, where *, ** and *** indicate p-values between 0.01 to 0.05, 0.001 to 0.01 and 0.0001 to 0.001 respectively. Bars and lines indicate mean and standard deviation. C) Pearson correlation analysis of CD161+ MAIT cell activation and CD161+ MAIT cell frequency of CD3+ T cells from the untreated high VL patient group. R2 quantifies goodness of fit to the non-linear regression (exponential grow equation). R2 is a fraction between 0.0 and 1.0, with 1.0 indicating the best fit.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4219715&req=5

pone-0111323-g003: Frequencies of activated CD161+ and CD161– TCR Vα7.2+ cells are elevated in the blood of highly viremic HIV patients.A) Plasma levels of sCD163, sCD14 and IL-18 were measured by ELISA in mostly corresponding samples of healthy controls (HC n = 13), highly viremic HIV-infected patients (high VL n = 18), patients receiving ART (ART n = 17), elite controllers (EC n = 6) and long-term nonprogressors (LTNP n = 6). B) Activated cells were defined as CD38+ and HLA-DR+ double positive cells and their frequency was assessed within the CD4–, MAIT and CD161–TCRVα7.2+ populations. PBMC samples were derived from healthy controls (HC), highly viremic HIV-infected patients (high VL), patients receiving ART (ART), elite controllers (EC) and long-term nonprogressors (LTNP). Groups were compared by Kruskal-Wallis test followed by Dunn's multiple comparison test. P-values smaller than 0.05 were considered significant, where *, ** and *** indicate p-values between 0.01 to 0.05, 0.001 to 0.01 and 0.0001 to 0.001 respectively. Bars and lines indicate mean and standard deviation. C) Pearson correlation analysis of CD161+ MAIT cell activation and CD161+ MAIT cell frequency of CD3+ T cells from the untreated high VL patient group. R2 quantifies goodness of fit to the non-linear regression (exponential grow equation). R2 is a fraction between 0.0 and 1.0, with 1.0 indicating the best fit.

Mentions: In accordance with previous reports [18], [19] we observed elevated levels of the soluble activation marker sCD163, a monocyte- and macrophage-specific scavenger receptor, shed during activation, in the plasma of untreated patients (Fig. 3A). A similar trend was observed for levels of sCD14, a marker of monocyte response to LPS [20]. However, this trend did not reach statistical significance and was not directly correlated to MAIT cell frequencies (Fig. 3A and data not shown).


CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

Eberhard JM, Hartjen P, Kummer S, Schmidt RE, Bockhorn M, Lehmann C, Balagopal A, Hauber J, van Lunzen J, Schulze zur Wiesch J - PLoS ONE (2014)

Frequencies of activated CD161+ and CD161– TCR Vα7.2+ cells are elevated in the blood of highly viremic HIV patients.A) Plasma levels of sCD163, sCD14 and IL-18 were measured by ELISA in mostly corresponding samples of healthy controls (HC n = 13), highly viremic HIV-infected patients (high VL n = 18), patients receiving ART (ART n = 17), elite controllers (EC n = 6) and long-term nonprogressors (LTNP n = 6). B) Activated cells were defined as CD38+ and HLA-DR+ double positive cells and their frequency was assessed within the CD4–, MAIT and CD161–TCRVα7.2+ populations. PBMC samples were derived from healthy controls (HC), highly viremic HIV-infected patients (high VL), patients receiving ART (ART), elite controllers (EC) and long-term nonprogressors (LTNP). Groups were compared by Kruskal-Wallis test followed by Dunn's multiple comparison test. P-values smaller than 0.05 were considered significant, where *, ** and *** indicate p-values between 0.01 to 0.05, 0.001 to 0.01 and 0.0001 to 0.001 respectively. Bars and lines indicate mean and standard deviation. C) Pearson correlation analysis of CD161+ MAIT cell activation and CD161+ MAIT cell frequency of CD3+ T cells from the untreated high VL patient group. R2 quantifies goodness of fit to the non-linear regression (exponential grow equation). R2 is a fraction between 0.0 and 1.0, with 1.0 indicating the best fit.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219715&req=5

pone-0111323-g003: Frequencies of activated CD161+ and CD161– TCR Vα7.2+ cells are elevated in the blood of highly viremic HIV patients.A) Plasma levels of sCD163, sCD14 and IL-18 were measured by ELISA in mostly corresponding samples of healthy controls (HC n = 13), highly viremic HIV-infected patients (high VL n = 18), patients receiving ART (ART n = 17), elite controllers (EC n = 6) and long-term nonprogressors (LTNP n = 6). B) Activated cells were defined as CD38+ and HLA-DR+ double positive cells and their frequency was assessed within the CD4–, MAIT and CD161–TCRVα7.2+ populations. PBMC samples were derived from healthy controls (HC), highly viremic HIV-infected patients (high VL), patients receiving ART (ART), elite controllers (EC) and long-term nonprogressors (LTNP). Groups were compared by Kruskal-Wallis test followed by Dunn's multiple comparison test. P-values smaller than 0.05 were considered significant, where *, ** and *** indicate p-values between 0.01 to 0.05, 0.001 to 0.01 and 0.0001 to 0.001 respectively. Bars and lines indicate mean and standard deviation. C) Pearson correlation analysis of CD161+ MAIT cell activation and CD161+ MAIT cell frequency of CD3+ T cells from the untreated high VL patient group. R2 quantifies goodness of fit to the non-linear regression (exponential grow equation). R2 is a fraction between 0.0 and 1.0, with 1.0 indicating the best fit.
Mentions: In accordance with previous reports [18], [19] we observed elevated levels of the soluble activation marker sCD163, a monocyte- and macrophage-specific scavenger receptor, shed during activation, in the plasma of untreated patients (Fig. 3A). A similar trend was observed for levels of sCD14, a marker of monocyte response to LPS [20]. However, this trend did not reach statistical significance and was not directly correlated to MAIT cell frequencies (Fig. 3A and data not shown).

Bottom Line: Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163.CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment.In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6.

View Article: PubMed Central - PubMed

Affiliation: Infectious Diseases Unit, Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.

ABSTRACT
Mucosal-associated invariant T (MAIT) cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR) Vα7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161(+) MAIT and CD161-TCRVα7.2(+) T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after in vitro stimulation with different cytokines and/or fixed E.coli. Reduced numbers of CD161(+) MAIT cells during HIV infection were detectable in the blood and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment. The loss of CD161(+) MAIT cells was correlated with higher levels of MAIT cell activation; an increased frequency of the CD161-TCRVα7.2(+)T cell subset in HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the irreversible reduction of the CD161(+) MAIT cell subset seems to be an early event in HIV infection that is independent of later stages of the disease. This loss appears to be at least partially due to the distinctive vulnerability of MAIT cells to the pronounced stimulation by microbial products and cytokines during HIV-infection.

Show MeSH
Related in: MedlinePlus