Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ.
<h4>Background</h4>Two different Th2 subsets have been defined recently on the basis of IL-5 expression - an IL-5(+)Th2 subset and an IL-5(-)Th2 subset in the setting of allergy. However, the role of these newly described CD4(+) T cells subpopulations has not been explored in other conte...
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oai:doaj.org-article:da18b081ab5b4f7f918f568fb5dbcaa02021-11-18T09:16:27ZParasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ.1935-27271935-273510.1371/journal.pntd.0002658https://doaj.org/article/da18b081ab5b4f7f918f568fb5dbcaa02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24498448/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Two different Th2 subsets have been defined recently on the basis of IL-5 expression - an IL-5(+)Th2 subset and an IL-5(-)Th2 subset in the setting of allergy. However, the role of these newly described CD4(+) T cells subpopulations has not been explored in other contexts.<h4>Methods</h4>To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5(+)IL-4(+)IL-13(+) CD4(+) T cells and IL-5(-)IL-4 IL-13(+) CD4(+) T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (Fo) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).<h4>Results</h4>INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced Fo of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the Fo of IL-5(+)Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4(+)IL-5(-)Th2 subpopulation and the levels of parasite antigen - specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased Fo of both Th2 subsets.<h4>Conclusions</h4>Our findings suggest that both IL-5(+) and IL-5(-)Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes.Rajamanickam AnuradhaParakkal Jovvian GeorgeLuke E HannaVedachalam ChandrasekaranP Paul KumaranThomas B NutmanSubash BabuPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 8, Iss 1, p e2658 (2014) |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Rajamanickam Anuradha Parakkal Jovvian George Luke E Hanna Vedachalam Chandrasekaran P Paul Kumaran Thomas B Nutman Subash Babu Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. |
description |
<h4>Background</h4>Two different Th2 subsets have been defined recently on the basis of IL-5 expression - an IL-5(+)Th2 subset and an IL-5(-)Th2 subset in the setting of allergy. However, the role of these newly described CD4(+) T cells subpopulations has not been explored in other contexts.<h4>Methods</h4>To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5(+)IL-4(+)IL-13(+) CD4(+) T cells and IL-5(-)IL-4 IL-13(+) CD4(+) T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (Fo) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).<h4>Results</h4>INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced Fo of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the Fo of IL-5(+)Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4(+)IL-5(-)Th2 subpopulation and the levels of parasite antigen - specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased Fo of both Th2 subsets.<h4>Conclusions</h4>Our findings suggest that both IL-5(+) and IL-5(-)Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes. |
format |
article |
author |
Rajamanickam Anuradha Parakkal Jovvian George Luke E Hanna Vedachalam Chandrasekaran P Paul Kumaran Thomas B Nutman Subash Babu |
author_facet |
Rajamanickam Anuradha Parakkal Jovvian George Luke E Hanna Vedachalam Chandrasekaran P Paul Kumaran Thomas B Nutman Subash Babu |
author_sort |
Rajamanickam Anuradha |
title |
Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. |
title_short |
Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. |
title_full |
Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. |
title_fullStr |
Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. |
title_full_unstemmed |
Parasite-antigen driven expansion of IL-5(-) and IL-5(+) Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGFβ. |
title_sort |
parasite-antigen driven expansion of il-5(-) and il-5(+) th2 human subpopulations in lymphatic filariasis and their differential dependence on il-10 and tgfβ. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doaj.org/article/da18b081ab5b4f7f918f568fb5dbcaa0 |
work_keys_str_mv |
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