Functional Profile of Antigen Specific CD4 T Cells in the Immune Response to Phospholipase A1 Allergen from Venom.

Luís Gustavo Romani Fernandes, Amilcar Perez-Riverol, Murilo Luiz Bazon, Débora Moitinho Abram, Márcia Regina Brochetto-Braga, Ricardo de Lima Zollner
Author Information
  1. Luís Gustavo Romani Fernandes: Laboratory of Translational Immunology, Medicine School, FCM, University of Campinas (UNICAMP), Campinas 13083-888, Brazil.
  2. Amilcar Perez-Riverol: Center of the Study of Social Insects, Department of General and Applied Biology, Institute of Biosciences of Rio Claro, Institute of Biosciences of Rio Claro, São Paulo State University, Rio Claro 13500, Brazil.
  3. Murilo Luiz Bazon: Laboratory of Arthropods Molecular Biology-LBMA-IBRC-UNESP (São Paulo State University), Rio Claro 13506-900, Brazil.
  4. Débora Moitinho Abram: Laboratory of Translational Immunology, Medicine School, FCM, University of Campinas (UNICAMP), Campinas 13083-888, Brazil.
  5. Márcia Regina Brochetto-Braga: Laboratory of Arthropods Molecular Biology-LBMA-IBRC-UNESP (São Paulo State University), Rio Claro 13506-900, Brazil.
  6. Ricardo de Lima Zollner: Laboratory of Translational Immunology, Medicine School, FCM, University of Campinas (UNICAMP), Campinas 13083-888, Brazil.

Abstract

Insect venom can cause systemic allergic reactions, including anaphylaxis. Improvements in diagnosis and venom immunotherapy (VIT) are based on a better understanding of an immunological response triggered by venom allergens. Previously, we demonstrated that the recombinant phospholipase A1 (rPoly p 1) from wasp venom induces specific IgE and IgG antibodies in sensitized mice, which recognized the native allergen. Here, we addressed the T cell immune response of rPoly p 1-sensitized BALB/c mice. Cultures of splenocytes were stimulated with venom extract and the proliferation of CD8 and CD4 T cells and the frequency of T regulatory cells (Tregs) populations were assessed by flow cytometry. Cytokines were quantified in cell culture supernatants in ELISA assays. The in vitro stimulation of T cells from sensitized mice induces a significant proliferation of CD4 T cells, but not of CD8 T cells. The cytokine pattern showed a high concentration of IFN-γ and IL-6, and no significant differences to IL-4, IL-1β and TGF-β1 production. In addition, the rPoly p 1 group showed a pronounced expansion of CD4CD25FoxP3 and CD4CD25FoxP3 Tregs. rPoly p 1 sensitization induces a Th1/Treg profile in CD4 T cell subset, suggesting its potential use in wasp venom immunotherapy.

Keywords

References

  1. Nat Rev Immunol. 2006 Oct;6(10):761-71 [PMID: 16998509]
  2. J Biol Chem. 1995 Mar 3;270(9):4457-65 [PMID: 7876212]
  3. Protein Pept Lett. 2012 Jun 1;19(6):625-35 [PMID: 22519534]
  4. FEMS Immunol Med Microbiol. 2012 Apr;64(3):413-24 [PMID: 22211712]
  5. Toxins (Basel). 2015 Jul 09;7(7):2551-70 [PMID: 26184309]
  6. Allergo J Int. 2017;26(3):93-105 [PMID: 28503403]
  7. Toxicon. 2018 Jun 15;148:172-196 [PMID: 29715467]
  8. Curr Opin Allergy Clin Immunol. 2017 Oct;17(5):363-372 [PMID: 28759475]
  9. Curr Biol. 2017 Apr 3;27(7):1013-1018 [PMID: 28343967]
  10. J Immunol. 2011 Jan 1;186(1):32-40 [PMID: 21106853]
  11. Clin Exp Allergy. 2005 Mar;35(3):367-73 [PMID: 15784117]
  12. Toxicon. 2016 Dec 15;124:44-52 [PMID: 27826019]
  13. Ann Allergy Asthma Immunol. 2014 Mar;112(3):195-9 [PMID: 24565594]
  14. Allergy. 2017 Mar;72(3):342-365 [PMID: 28120424]
  15. Front Immunol. 2019 Aug 21;10:1959 [PMID: 31497015]
  16. Curr Opin Allergy Clin Immunol. 2002 Aug;2(4):341-6 [PMID: 12130949]
  17. Clinics (Sao Paulo). 2011;66(6):943-7 [PMID: 21808856]
  18. J Immunol. 1995 Jan 15;154(2):577-84 [PMID: 7814869]
  19. Immunol Rev. 2017 Jul;278(1):219-236 [PMID: 28658547]
  20. World Allergy Organ J. 2015 May 14;8(1):17 [PMID: 26023323]
  21. Immunology. 2003 Nov;110(3):376-85 [PMID: 14632666]
  22. Toxicon. 2013 Mar 15;64:70-80 [PMID: 23305623]
  23. Immunol Allergy Clin North Am. 2015 May;35(2):287-302 [PMID: 25841552]
  24. J Immunol. 2006 Jun 1;176(11):6586-93 [PMID: 16709816]
  25. J Immunol Res. 2018 Jun 14;2018:6012053 [PMID: 30013991]
  26. Toxicon. 2007 Dec 1;50(7):923-37 [PMID: 17761205]
  27. Mol Immunol. 2018 Jan;93:87-93 [PMID: 29156294]
  28. J Allergy Clin Immunol. 2014 Mar;133(3):621-31 [PMID: 24581429]
  29. J Proteome Res. 2014 Feb 7;13(2):855-65 [PMID: 24308509]
  30. J Allergy Clin Immunol. 2011 Feb;127(2):495-501.e1-6 [PMID: 21195472]
  31. Allergy. 2000 Nov;55(11):1005-10 [PMID: 11097308]
  32. J Proteomics. 2017 May 24;161:88-103 [PMID: 28435107]

Grants

  1. 455422/2014-1/Conselho Nacional de Desenvolvimento Científico e Tecnológico
  2. 2019/00729-7 to LGRF; 2014/13936-7 to MRBB; 2017/22405-3 to APR/Fundação de Amparo à Pesquisa do Estado de São Paulo
  3. Postgraduate scholarships/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

MeSH Term

Allergens
Animals
CD4-Positive T-Lymphocytes
Cell Proliferation
Cells, Cultured
Cytokines
Desensitization, Immunologic
Female
Hypersensitivity
Insect Bites and Stings
Insect Proteins
Lymphocyte Activation
Mice, Inbred BALB C
Phospholipases A1
Wasp Venoms

Chemicals

Allergens
Cytokines
Insect Proteins
Wasp Venoms
Phospholipases A1

Word Cloud

Created with Highcharts 10.0.0TvenomcellsrPolypCD41inducesmicecellimmunotherapyresponseA1waspsensitizedproliferationCD8TregssignificantshowedCD4CD25FoxP3InsectcancausesystemicallergicreactionsincludinganaphylaxisImprovementsdiagnosisVITbasedbetterunderstandingimmunologicaltriggeredallergensPreviouslydemonstratedrecombinantphospholipasespecificIgEIgGantibodiesrecognizednativeallergenaddressedimmune1-sensitizedBALB/cCulturessplenocytesstimulatedextractfrequencyregulatorypopulationsassessedflowcytometryCytokinesquantifiedculturesupernatantsELISAassaysvitrostimulationcytokinepatternhighconcentrationIFN-γIL-6differencesIL-4IL-1βTGF-β1productionadditiongrouppronouncedexpansionsensitizationTh1/TregprofilesubsetsuggestingpotentialuseFunctionalProfileAntigenSpecificCellsImmuneResponsePhospholipaseAllergenVenomCD4+HymenopteraallergyPolybiapaulista

Similar Articles

Cited By