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Regulatory and activated T cells in human Schistosoma haematobium infections.

Nausch N, Midzi N, Mduluza T, Maizels RM, Mutapi F - PLoS ONE (2011)

Bottom Line: Acquired immunity against helminths is characterised by a complex interplay between the effector Th1 and Th2 immune responses and it slowly manifests with age as a result of cumulative exposure to parasite antigens.The relative proportions of regulatory T cells differ significantly between young individuals in whom high infection is associated with an enhanced regulatory phenotype and older infected patients in whom the regulatory response is attenuated.This may influence or reflect different stages of the development of protective schistosome acquired immunity and immunopathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Ashworth Laboratories, School of Biological Sciences, Institute for Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom. nnausch@staffmail.ed.ac.uk

ABSTRACT
Acquired immunity against helminths is characterised by a complex interplay between the effector Th1 and Th2 immune responses and it slowly manifests with age as a result of cumulative exposure to parasite antigens. Data from experimental models suggest that immunity is also influenced by regulatory T cells (Treg), but as yet studies on Treg in human schistosome infections are limited. This study investigated the relationship between schistosome infection intensity and the two cell populations regulatory T cells (TREG: CD4(+(dim))CD25(+(high))FOXP3(+)CD127(low)), and activated (Tact: CD4(+)CD25(+)FOXP3(-)) T cells in Zimbabweans exposed to Schistosoma haematobium parasites. Participants were partitioned into two age groups, young children (8-13 years) in whom schistosome infection levels were rising to peak and older people (14+ years) with declining infection levels. The relationship between Tact proportions and schistosome infection intensity remained unchanged with age. However Treg proportions rose significantly with increasing infection in the younger age group. In contrast Treg were negatively correlated to infection intensity in the older age group. The relative proportions of regulatory T cells differ significantly between young individuals in whom high infection is associated with an enhanced regulatory phenotype and older infected patients in whom the regulatory response is attenuated. This may influence or reflect different stages of the development of protective schistosome acquired immunity and immunopathogenesis.

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Treg and Tact are distinguished by a combination of several markers.(A) PBMC were electronically gated on lymphocyte population (left panel) followed by gate on total CD4+ cells (middle panel). CD4+ cells were analysed for the expression of CD25 and CD127 (right panel). (A–C) CD25+FOXP3+ cells were identified as Treg, whereas CD25+FOXP3− counted as Tact. A dot plot for one individual is shown for group 1 (B) and group 2 (C). Gating on Treg and Tact subsets was verified by further analysis of level of expression of CD25 (B–C, middle panel) and CD127 (B–C, right panel) expressed on Treg (red) and Tact (green). Gray line - isotype control.
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pone-0016860-g002: Treg and Tact are distinguished by a combination of several markers.(A) PBMC were electronically gated on lymphocyte population (left panel) followed by gate on total CD4+ cells (middle panel). CD4+ cells were analysed for the expression of CD25 and CD127 (right panel). (A–C) CD25+FOXP3+ cells were identified as Treg, whereas CD25+FOXP3− counted as Tact. A dot plot for one individual is shown for group 1 (B) and group 2 (C). Gating on Treg and Tact subsets was verified by further analysis of level of expression of CD25 (B–C, middle panel) and CD127 (B–C, right panel) expressed on Treg (red) and Tact (green). Gray line - isotype control.

Mentions: CD4+ lymphocytes were analyzed for the expression of CD25, FOXP3 and CD127 (Figure 2A) and gated on either CD4+CD25+FOXP+ (Treg) or CD4+CD25+FOXP− (Tact) subsets (Figure 2B, C). CD25+FOXP3+ Treg expressed CD25 at high levels and showed a clear CD127low, CD4dim phenotype, allowing the identification of Treg as CD4+(dim)CD25+(high)FOXP3+CD127low cells (Figure 2A–C). In contrast Tact, identified as CD4+CD25+FOXP3− cells, showed lower CD25 expression compared to the FOXP3+ cells. In addition most Tact expressed high levels of CD127 and normal levels of CD4. The expression of CD25high, CD4low, CD127dim and FOXP3 were significantly correlated to each other (data not shown), and hence this combination of markers was used to discriminate between Tact and Treg populations.


Regulatory and activated T cells in human Schistosoma haematobium infections.

Nausch N, Midzi N, Mduluza T, Maizels RM, Mutapi F - PLoS ONE (2011)

Treg and Tact are distinguished by a combination of several markers.(A) PBMC were electronically gated on lymphocyte population (left panel) followed by gate on total CD4+ cells (middle panel). CD4+ cells were analysed for the expression of CD25 and CD127 (right panel). (A–C) CD25+FOXP3+ cells were identified as Treg, whereas CD25+FOXP3− counted as Tact. A dot plot for one individual is shown for group 1 (B) and group 2 (C). Gating on Treg and Tact subsets was verified by further analysis of level of expression of CD25 (B–C, middle panel) and CD127 (B–C, right panel) expressed on Treg (red) and Tact (green). Gray line - isotype control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3037381&req=5

pone-0016860-g002: Treg and Tact are distinguished by a combination of several markers.(A) PBMC were electronically gated on lymphocyte population (left panel) followed by gate on total CD4+ cells (middle panel). CD4+ cells were analysed for the expression of CD25 and CD127 (right panel). (A–C) CD25+FOXP3+ cells were identified as Treg, whereas CD25+FOXP3− counted as Tact. A dot plot for one individual is shown for group 1 (B) and group 2 (C). Gating on Treg and Tact subsets was verified by further analysis of level of expression of CD25 (B–C, middle panel) and CD127 (B–C, right panel) expressed on Treg (red) and Tact (green). Gray line - isotype control.
Mentions: CD4+ lymphocytes were analyzed for the expression of CD25, FOXP3 and CD127 (Figure 2A) and gated on either CD4+CD25+FOXP+ (Treg) or CD4+CD25+FOXP− (Tact) subsets (Figure 2B, C). CD25+FOXP3+ Treg expressed CD25 at high levels and showed a clear CD127low, CD4dim phenotype, allowing the identification of Treg as CD4+(dim)CD25+(high)FOXP3+CD127low cells (Figure 2A–C). In contrast Tact, identified as CD4+CD25+FOXP3− cells, showed lower CD25 expression compared to the FOXP3+ cells. In addition most Tact expressed high levels of CD127 and normal levels of CD4. The expression of CD25high, CD4low, CD127dim and FOXP3 were significantly correlated to each other (data not shown), and hence this combination of markers was used to discriminate between Tact and Treg populations.

Bottom Line: Acquired immunity against helminths is characterised by a complex interplay between the effector Th1 and Th2 immune responses and it slowly manifests with age as a result of cumulative exposure to parasite antigens.The relative proportions of regulatory T cells differ significantly between young individuals in whom high infection is associated with an enhanced regulatory phenotype and older infected patients in whom the regulatory response is attenuated.This may influence or reflect different stages of the development of protective schistosome acquired immunity and immunopathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Ashworth Laboratories, School of Biological Sciences, Institute for Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom. nnausch@staffmail.ed.ac.uk

ABSTRACT
Acquired immunity against helminths is characterised by a complex interplay between the effector Th1 and Th2 immune responses and it slowly manifests with age as a result of cumulative exposure to parasite antigens. Data from experimental models suggest that immunity is also influenced by regulatory T cells (Treg), but as yet studies on Treg in human schistosome infections are limited. This study investigated the relationship between schistosome infection intensity and the two cell populations regulatory T cells (TREG: CD4(+(dim))CD25(+(high))FOXP3(+)CD127(low)), and activated (Tact: CD4(+)CD25(+)FOXP3(-)) T cells in Zimbabweans exposed to Schistosoma haematobium parasites. Participants were partitioned into two age groups, young children (8-13 years) in whom schistosome infection levels were rising to peak and older people (14+ years) with declining infection levels. The relationship between Tact proportions and schistosome infection intensity remained unchanged with age. However Treg proportions rose significantly with increasing infection in the younger age group. In contrast Treg were negatively correlated to infection intensity in the older age group. The relative proportions of regulatory T cells differ significantly between young individuals in whom high infection is associated with an enhanced regulatory phenotype and older infected patients in whom the regulatory response is attenuated. This may influence or reflect different stages of the development of protective schistosome acquired immunity and immunopathogenesis.

Show MeSH
Related in: MedlinePlus