PAS-1, an Ascaris suum protein, modulates allergic airway inflammation via CD8+γδTCR+ and CD4+CD25+FoxP3+ T cells.
We have previously demonstrated that PAS-1, a 200 kDa protein from Ascaris suum, has a potent immunomodulatory effect on humoral and cell-mediated responses induced by APAS-3 (an allergenic protein from A. suum) or unrelated antigens. In this study, we investigated the mechanisms by which PAS-1 is able to induce this effect on an allergic airway inflammation induced by OVA in mice. C57BL/6 mice were adoptively transferred on day 0 with seven different PAS-1-primed cell populations: PAS-1-primed CD19(+) or B220(+) or CD3(+) or CD4(+) or CD8(+) or CD4(+) CD25⁻ or CD4(+) CD25(+) lymphocytes. These mice were immunized twice with OVA and alum by intraperitoneal route (days 0 and 7) and challenged twice by intranasal route (days 14 and 21). Two days after the last challenge, the airway inflammation was evaluated by antibody levels, cellular migration, eosinophil peroxidase levels, cytokine and eotaxin production, and pulmonary mechanical parameters. Among the adoptively transferred primed lymphocytes, only CD4(+) CD25(+) , CD8(+) or the combination of both T cells impaired the production of total IgE and OVA-specific IgE and IgG1 antibodies, eosinophilic airway inflammation, Th2-type cytokines (IL-4, IL-5 and IL-13), eotaxin release and airway hyperreactivity. Moreover, airway recruited cells from CD4(+) CD25(+) and CD8(+) T-cell recipient secreted more IL-10/TGF-β and IFN-γ, respectively. Moreover, we found that PAS-1 expands significantly the number of CD4(+) CD25(+) FoxP3(+) and CD8(+) γδTCR(+) cells. In conclusion, these findings demonstrate that the immunomodulatory effect of PAS-1 is mediated by these T-cell subsets.
Laboratory of Immunopathology, Butantan Institute, São Paulo, Brazil.
C A A
CA
de Araújo
A
A
Perini
M A
MA
Martins
M S
MS
Macedo
M F
MF
Macedo-Soares
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D015801:Helminth Proteins / Q000276:immunology*; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015801:Helminth Proteins; D053645:Interleukin-2 Receptor alpha Subunit; C511899:PAS-1 protein, Ascaris suum; D016692:Receptors, Antigen, T-Cell, gamma-delta