Critical role of NKT cells in posttransplant alloantibody production

J. M. Zimmerer, P. Swamy, P. B. Sanghavi, C. L. Wright, M. Abdel-Rasoul, S. M. Elzein, Randy Brutkiewicz, G. L. Bumgardner

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli. Using a murine transplant model, the authors report a novel type I natural killer T cell-mediated mechanism that enhances the magnitude of IgG1 alloantibody production posttransplant.

Original languageEnglish
Pages (from-to)2491-2499
Number of pages9
JournalAmerican Journal of Transplantation
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2014

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Isoantibodies
Natural Killer T-Cells
Interleukin-4
Immunoglobulin G
T-Lymphocytes
Interferons
Antibody Formation
B-Lymphocytes
Transplants

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Zimmerer, J. M., Swamy, P., Sanghavi, P. B., Wright, C. L., Abdel-Rasoul, M., Elzein, S. M., ... Bumgardner, G. L. (2014). Critical role of NKT cells in posttransplant alloantibody production. American Journal of Transplantation, 14(11), 2491-2499. https://doi.org/10.1111/ajt.12922

Critical role of NKT cells in posttransplant alloantibody production. / Zimmerer, J. M.; Swamy, P.; Sanghavi, P. B.; Wright, C. L.; Abdel-Rasoul, M.; Elzein, S. M.; Brutkiewicz, Randy; Bumgardner, G. L.

In: American Journal of Transplantation, Vol. 14, No. 11, 01.11.2014, p. 2491-2499.

Research output: Contribution to journalArticle

Zimmerer, JM, Swamy, P, Sanghavi, PB, Wright, CL, Abdel-Rasoul, M, Elzein, SM, Brutkiewicz, R & Bumgardner, GL 2014, 'Critical role of NKT cells in posttransplant alloantibody production', American Journal of Transplantation, vol. 14, no. 11, pp. 2491-2499. https://doi.org/10.1111/ajt.12922
Zimmerer JM, Swamy P, Sanghavi PB, Wright CL, Abdel-Rasoul M, Elzein SM et al. Critical role of NKT cells in posttransplant alloantibody production. American Journal of Transplantation. 2014 Nov 1;14(11):2491-2499. https://doi.org/10.1111/ajt.12922
Zimmerer, J. M. ; Swamy, P. ; Sanghavi, P. B. ; Wright, C. L. ; Abdel-Rasoul, M. ; Elzein, S. M. ; Brutkiewicz, Randy ; Bumgardner, G. L. / Critical role of NKT cells in posttransplant alloantibody production. In: American Journal of Transplantation. 2014 ; Vol. 14, No. 11. pp. 2491-2499.
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