Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients.
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.
Dutra
Walderez O
WO
Departamento de Bioquímica-Imunologia, ICB-UFMG, Belo Horizonte, MG, Brazil. waldutra@mono.icb.ufmg.br
Correa-Oliveira
Rodrigo
R
Dunne
David
D
Cecchini
Luiza Fosenca
LF
Fraga
Lúcia
L
Roberts
Morven
M
Soares-Silveira
Alda Maria
AM
Webster
Michelle
M
Yssel
Hans
H
Gollob
Kenneth J
KJ
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007376:Interleukin-2; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma