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Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38(-) T cells in HIV-exposed uninfected subjects.

Oliveira LM, Lima JF, Cervantes CA, Casseb JS, Mendonça M, Duarte AJ, Sato MN - Sci Rep (2015)

Bottom Line: EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24.EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile.These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, Brazil.

ABSTRACT
Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38- T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.

No MeSH data available.


Related in: MedlinePlus

Presence of circulating Th22 and Tc22 cells in EUs and HIV-1-infected subjects.PBMCs of HCs (n = 15), EUs (n = 16) and HIV-infected individuals (n = 15) were cultivated with medium (baseline), HIV Gag peptide pools [Gag1 (p17), Gag2 (p24), and Gag3 (p15)], or SEB for 6 h and Brefeldin A for 4 h. Th22 and Tc22 cell frequencies were obtained by excluding IFN-γ and IL-17a. (A) Th22 and (B) Tc22 cell frequencies were assessed using flow cytometry. Frequencies of Th22 or Tc22 cells were subtracted from baseline levels. The results are shown as medians and IQRs. *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001, adjusted for multiple comparisons.
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f2: Presence of circulating Th22 and Tc22 cells in EUs and HIV-1-infected subjects.PBMCs of HCs (n = 15), EUs (n = 16) and HIV-infected individuals (n = 15) were cultivated with medium (baseline), HIV Gag peptide pools [Gag1 (p17), Gag2 (p24), and Gag3 (p15)], or SEB for 6 h and Brefeldin A for 4 h. Th22 and Tc22 cell frequencies were obtained by excluding IFN-γ and IL-17a. (A) Th22 and (B) Tc22 cell frequencies were assessed using flow cytometry. Frequencies of Th22 or Tc22 cells were subtracted from baseline levels. The results are shown as medians and IQRs. *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001, adjusted for multiple comparisons.

Mentions: Next, to verify whether the IL-22 response of CD4+ T cells was related to Th22 cells, we evaluated IL-22 expression, excluding IFN-γ- and IL-17 secreting cells in CD4+ T cells as previously described, to identify Th22 cells. The gating strategy is shown in Supplementary Figure 2. Curiously, p15-specific stimulation induced increased frequencies of Th22 cells in both HIV-1 and EU subjects compared to the HC group (Fig. 2A), and p24 induced Th22 expansion in HIV-1 individuals (Fig. 2A). Again, an increased frequency of Th22 cells was induced only in the EU group with SEB stimulation.


Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38(-) T cells in HIV-exposed uninfected subjects.

Oliveira LM, Lima JF, Cervantes CA, Casseb JS, Mendonça M, Duarte AJ, Sato MN - Sci Rep (2015)

Presence of circulating Th22 and Tc22 cells in EUs and HIV-1-infected subjects.PBMCs of HCs (n = 15), EUs (n = 16) and HIV-infected individuals (n = 15) were cultivated with medium (baseline), HIV Gag peptide pools [Gag1 (p17), Gag2 (p24), and Gag3 (p15)], or SEB for 6 h and Brefeldin A for 4 h. Th22 and Tc22 cell frequencies were obtained by excluding IFN-γ and IL-17a. (A) Th22 and (B) Tc22 cell frequencies were assessed using flow cytometry. Frequencies of Th22 or Tc22 cells were subtracted from baseline levels. The results are shown as medians and IQRs. *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001, adjusted for multiple comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561954&req=5

f2: Presence of circulating Th22 and Tc22 cells in EUs and HIV-1-infected subjects.PBMCs of HCs (n = 15), EUs (n = 16) and HIV-infected individuals (n = 15) were cultivated with medium (baseline), HIV Gag peptide pools [Gag1 (p17), Gag2 (p24), and Gag3 (p15)], or SEB for 6 h and Brefeldin A for 4 h. Th22 and Tc22 cell frequencies were obtained by excluding IFN-γ and IL-17a. (A) Th22 and (B) Tc22 cell frequencies were assessed using flow cytometry. Frequencies of Th22 or Tc22 cells were subtracted from baseline levels. The results are shown as medians and IQRs. *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001, adjusted for multiple comparisons.
Mentions: Next, to verify whether the IL-22 response of CD4+ T cells was related to Th22 cells, we evaluated IL-22 expression, excluding IFN-γ- and IL-17 secreting cells in CD4+ T cells as previously described, to identify Th22 cells. The gating strategy is shown in Supplementary Figure 2. Curiously, p15-specific stimulation induced increased frequencies of Th22 cells in both HIV-1 and EU subjects compared to the HC group (Fig. 2A), and p24 induced Th22 expansion in HIV-1 individuals (Fig. 2A). Again, an increased frequency of Th22 cells was induced only in the EU group with SEB stimulation.

Bottom Line: EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24.EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile.These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, Brazil.

ABSTRACT
Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38- T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.

No MeSH data available.


Related in: MedlinePlus