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CD4+CD25hiFOXP3+ cells in cord blood of neonates born from filaria infected mother are negatively associated with CD4+Tbet+ and CD4+RORγt+ T cells.

Ateba-Ngoa U, Mombo-Ngoma G, Zettlmeissl E, van der Vlugt LE, de Jong SE, de Jong S, Matsiegui PB, Ramharter M, Kremsner PG, Yazdanbakhsh M, Adegnika AA - PLoS ONE (2014)

Bottom Line: At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3.No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells.However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively).

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherches Médicales de Lambaréné, BP 118, Lambaréné, Gabon; Department of Parasitology, Leiden University Medical Center, Albinusdreef 2 2333 ZA Leiden, The Netherlands; Institut für Tropenmedizin, Universität Tübingen, Wilhelmstraβe 27 D-72074 Tübingen, Germany.

ABSTRACT

Background: Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses.

Methodology: Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3.

Results: No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively).

Conclusion: Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.

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Related in: MedlinePlus

The relation between CD4+CD25hiFOXP3+ T cells and CD4+Tbet+ (upper panel) as well as CD4+CD25hiFOXP3+ T cells and CD4+RORγT+ T cells (lower panel) of CBMC of neonates from filaria negative (in grey) and filaria positive (in black) mothers assessed by a linear regression analysis.Each dot shows value from a single subject while the solid lines represent the regression lines of the model. The strength of the association between two variables is given by the value of the regression coefficient beta (β) value in each graph. A positive β value indicates a positive association between the variables in the model while a negative β value indicates a negative association. P values are given to indicate the statistical significance of the associations.
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pone-0114630-g002: The relation between CD4+CD25hiFOXP3+ T cells and CD4+Tbet+ (upper panel) as well as CD4+CD25hiFOXP3+ T cells and CD4+RORγT+ T cells (lower panel) of CBMC of neonates from filaria negative (in grey) and filaria positive (in black) mothers assessed by a linear regression analysis.Each dot shows value from a single subject while the solid lines represent the regression lines of the model. The strength of the association between two variables is given by the value of the regression coefficient beta (β) value in each graph. A positive β value indicates a positive association between the variables in the model while a negative β value indicates a negative association. P values are given to indicate the statistical significance of the associations.

Mentions: In order to assess the association between regulatory T cells and the different T helper subsets, we examined the association between CD4+CD25hiFOXP3+ T cells and CD4+ Tbet+ T cells, CD4+RORγt+ T cells respectively through a linear regression analysis. Analyzing all subjects together, we observed a negative association between Treg and CD4+Tbet+T cells (B = −0.149, 95% CI = −0.256 to −0.043, p = 0.008) or CD4+RORγT+T cells (B = −0.175, 95% CI = −0.275 to −0.074, p = 0.001). Interestingly when stratifying our study subjects by their infectious status we observed that the negative association between CD4+CD25hiFOXP3+ Treg cells and the population of TH1 and TH17 cells was only significant in the offspring of microfilaria infected mothers (Fig. 2).


CD4+CD25hiFOXP3+ cells in cord blood of neonates born from filaria infected mother are negatively associated with CD4+Tbet+ and CD4+RORγt+ T cells.

Ateba-Ngoa U, Mombo-Ngoma G, Zettlmeissl E, van der Vlugt LE, de Jong SE, de Jong S, Matsiegui PB, Ramharter M, Kremsner PG, Yazdanbakhsh M, Adegnika AA - PLoS ONE (2014)

The relation between CD4+CD25hiFOXP3+ T cells and CD4+Tbet+ (upper panel) as well as CD4+CD25hiFOXP3+ T cells and CD4+RORγT+ T cells (lower panel) of CBMC of neonates from filaria negative (in grey) and filaria positive (in black) mothers assessed by a linear regression analysis.Each dot shows value from a single subject while the solid lines represent the regression lines of the model. The strength of the association between two variables is given by the value of the regression coefficient beta (β) value in each graph. A positive β value indicates a positive association between the variables in the model while a negative β value indicates a negative association. P values are given to indicate the statistical significance of the associations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4273973&req=5

pone-0114630-g002: The relation between CD4+CD25hiFOXP3+ T cells and CD4+Tbet+ (upper panel) as well as CD4+CD25hiFOXP3+ T cells and CD4+RORγT+ T cells (lower panel) of CBMC of neonates from filaria negative (in grey) and filaria positive (in black) mothers assessed by a linear regression analysis.Each dot shows value from a single subject while the solid lines represent the regression lines of the model. The strength of the association between two variables is given by the value of the regression coefficient beta (β) value in each graph. A positive β value indicates a positive association between the variables in the model while a negative β value indicates a negative association. P values are given to indicate the statistical significance of the associations.
Mentions: In order to assess the association between regulatory T cells and the different T helper subsets, we examined the association between CD4+CD25hiFOXP3+ T cells and CD4+ Tbet+ T cells, CD4+RORγt+ T cells respectively through a linear regression analysis. Analyzing all subjects together, we observed a negative association between Treg and CD4+Tbet+T cells (B = −0.149, 95% CI = −0.256 to −0.043, p = 0.008) or CD4+RORγT+T cells (B = −0.175, 95% CI = −0.275 to −0.074, p = 0.001). Interestingly when stratifying our study subjects by their infectious status we observed that the negative association between CD4+CD25hiFOXP3+ Treg cells and the population of TH1 and TH17 cells was only significant in the offspring of microfilaria infected mothers (Fig. 2).

Bottom Line: At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3.No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells.However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively).

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherches Médicales de Lambaréné, BP 118, Lambaréné, Gabon; Department of Parasitology, Leiden University Medical Center, Albinusdreef 2 2333 ZA Leiden, The Netherlands; Institut für Tropenmedizin, Universität Tübingen, Wilhelmstraβe 27 D-72074 Tübingen, Germany.

ABSTRACT

Background: Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses.

Methodology: Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3.

Results: No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively).

Conclusion: Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.

Show MeSH
Related in: MedlinePlus