title: Eosinophils are not required for the induction and maintenance of an alloantibody response.
abstract: Eosinophil-produced cytokines have been shown to participate in the maintenance of antigen-specific plasma cells (PC) in bone marrow (BM), suggesting that eosinophils are required in the development and/or maintenance of alloantibody responses posttransplant. To test this hypothesis, we sensitized eosinophil-deficient ΔdblGATA1 mice and wild-type (WT) control mice with allogeneic splenocytes or with allogeneic heart grafts and compared the kinetics and titers of serum donor-specific antibodies (DSA), as well as BM and spleen CD130 + B220 low PC populations between groups. Spleen cells from naïve ΔdblGATA1 BALB/c mice contained higher percentages of PC than WT without detectable differences in BM PCs. After sensitization with allogeneic splenocytes, BALB/c ΔdblGATA1 mice contained fewer BM PCs but more splenic PCs compared to controls. These differences were associated with modestly lower titers of serum DSA 4 and 12 weeks after sensitization but secondary immunizations induced similar increases in both groups. Moreover, the kinetics and strength of DSA did not differ in WT and ΔdblGATA1 BALB/c mice transplanted with B6 cardiac allografts, nor did they differ in transplanted ΔdblGATA1 and WT mice on a B6 background. Therefore, eosinophils are not required for alloantibody formation or maintenance in mice and are thus unlikely to be effective targets for antibody desensitization.
authors.affiliation: Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: P
authors.initials: P
authors.lastname: Cravedi
authors.forename: D A
authors.initials: DA
authors.lastname: Lessman
authors.forename: P S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000502:physiology*; D016027:Heart Transplantation; D007518:Isoantibodies / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D007518:Isoantibodies
keywords: Donor-specific antibodies; GATA-1; eosinophil; transplant
references.citation: J Exp Med. 2013 Feb 11;210(2):257-68
references.pmid: 23382542
references.citation: Blood. 2008 Mar 1;111(5):2755-64
references.pmid: 18180376
references.citation: J Exp Med. 2002 Jun 3;195(11):1387-95
references.pmid: 12045237
references.citation: Am J Transplant. 2007 Oct;7(10):2371-7
references.pmid: 17845571
references.citation: Clin J Am Soc Nephrol. 2006 May;1(3):433-40
references.pmid: 17699242
references.citation: Transpl Immunol. 2004 Jun-Jul;13(1):63-71
references.pmid: 15203130
references.citation: Nat Immunol. 2011 Feb;12(2):151-9
references.pmid: 21217761
references.citation: J Immunol. 2003 Aug 15;171(4):1684-90
references.pmid: 12902466
references.citation: Am J Transplant. 2007 Dec;7(12):2809-15
references.pmid: 17908268
references.citation: J Am Soc Nephrol. 2010 Aug;21(8):1398-406
references.pmid: 20634297
references.citation: Am J Transplant. 2011 Feb;11(2):312-9
references.pmid: 21219570
references.citation: Allergy. 2008 Sep;63(9):1156-63
references.pmid: 18699932