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Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients.

Dutra WO, Correa-Oliveira R, Dunne D, Cecchini LF, Fraga L, Roberts M, Soares-Silveira AM, Webster M, Yssel H, Gollob KJ - BMC Immunol. (2002)

Bottom Line: Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE.Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs.However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Bioquímica-Imunologia, ICB-UFMG, Belo Horizonte, MG, Brazil. waldutra@mono.icb.ufmg.br

ABSTRACT

Background: Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-gamma or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP.

Results: Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed.

Conclusions: High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-gamma.

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Th1 and Th2 cytokines are made by separate, Th1 and Th2 like cells, not by double producing, Th0 cells. Representative cytokine production (IL-4 and IFN-γ or IL-5 and IL-2) of total gated lymphocytes from high (A-C) or low IgE-producers (D-F). Isotype controls show the lack of non-specific staining (A and D). The absence of double producing, IL-4+/IFN-γ+, lymphocytes is evident in the high IgE group (B), with essentially all IL-4 producing cells being negative for IFN-γ production. In all cases, there is a clear segregation of IL-4 and IFN-γ producing cells (B and E), or of IL-5 and IL-2 producing cells (C and F).
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Figure 3: Th1 and Th2 cytokines are made by separate, Th1 and Th2 like cells, not by double producing, Th0 cells. Representative cytokine production (IL-4 and IFN-γ or IL-5 and IL-2) of total gated lymphocytes from high (A-C) or low IgE-producers (D-F). Isotype controls show the lack of non-specific staining (A and D). The absence of double producing, IL-4+/IFN-γ+, lymphocytes is evident in the high IgE group (B), with essentially all IL-4 producing cells being negative for IFN-γ production. In all cases, there is a clear segregation of IL-4 and IFN-γ producing cells (B and E), or of IL-5 and IL-2 producing cells (C and F).

Mentions: In order to gain a better understanding of the immunoregulation and balance of cytokine production in these individuals, we performed single cell cytoplasmic staining using two pairs of labeled antibodies as described in Materials and Methods. Figure 3 shows a representative dot-plot of cytokine production by lymphocytes of high (A-C) and low (D-F) -anti-SWAP IgE responders, demonstrating the clearly defined cytokine-producing cell populations. Moreover, it can be seen that greater than 90% of the IL-4 producing cells are polarized Th2 like cells, with little contribution from Th0 cells as indicated by the lack of double positive lymphocytes producing both IL-4 and IFN-γ (Figure 3B), confirming the polarization of Th2 type cells in these individuals.


Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients.

Dutra WO, Correa-Oliveira R, Dunne D, Cecchini LF, Fraga L, Roberts M, Soares-Silveira AM, Webster M, Yssel H, Gollob KJ - BMC Immunol. (2002)

Th1 and Th2 cytokines are made by separate, Th1 and Th2 like cells, not by double producing, Th0 cells. Representative cytokine production (IL-4 and IFN-γ or IL-5 and IL-2) of total gated lymphocytes from high (A-C) or low IgE-producers (D-F). Isotype controls show the lack of non-specific staining (A and D). The absence of double producing, IL-4+/IFN-γ+, lymphocytes is evident in the high IgE group (B), with essentially all IL-4 producing cells being negative for IFN-γ production. In all cases, there is a clear segregation of IL-4 and IFN-γ producing cells (B and E), or of IL-5 and IL-2 producing cells (C and F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC117775&req=5

Figure 3: Th1 and Th2 cytokines are made by separate, Th1 and Th2 like cells, not by double producing, Th0 cells. Representative cytokine production (IL-4 and IFN-γ or IL-5 and IL-2) of total gated lymphocytes from high (A-C) or low IgE-producers (D-F). Isotype controls show the lack of non-specific staining (A and D). The absence of double producing, IL-4+/IFN-γ+, lymphocytes is evident in the high IgE group (B), with essentially all IL-4 producing cells being negative for IFN-γ production. In all cases, there is a clear segregation of IL-4 and IFN-γ producing cells (B and E), or of IL-5 and IL-2 producing cells (C and F).
Mentions: In order to gain a better understanding of the immunoregulation and balance of cytokine production in these individuals, we performed single cell cytoplasmic staining using two pairs of labeled antibodies as described in Materials and Methods. Figure 3 shows a representative dot-plot of cytokine production by lymphocytes of high (A-C) and low (D-F) -anti-SWAP IgE responders, demonstrating the clearly defined cytokine-producing cell populations. Moreover, it can be seen that greater than 90% of the IL-4 producing cells are polarized Th2 like cells, with little contribution from Th0 cells as indicated by the lack of double positive lymphocytes producing both IL-4 and IFN-γ (Figure 3B), confirming the polarization of Th2 type cells in these individuals.

Bottom Line: Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE.Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs.However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Bioquímica-Imunologia, ICB-UFMG, Belo Horizonte, MG, Brazil. waldutra@mono.icb.ufmg.br

ABSTRACT

Background: Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP) IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-gamma or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP.

Results: Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed.

Conclusions: High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-gamma.

Show MeSH
Related in: MedlinePlus