Critical Role of NKT Cells in Posttransplant Alloantibody Production

Overview

Journal Am J Transplant

Publisher Elsevier

Specialty General Surgery

Date 2014 Sep 16

PMID 25220596

Citations 5

Authors

J M Zimmerer

P Swamy

P B Sanghavi

C L Wright

M Abdel-Rasoul

S M Elzein

R R Brutkiewicz

G L Bumgardner

Affiliations

Soon will be listed here.

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.

Citing Articles

Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity.

Umeshappa C, Sole P, Yamanouchi J, Mohapatra S, Surewaard B, Garnica J Nat Commun. 2022; 13(1):3279.

PMID: 35672409 PMC: 9174212. DOI: 10.1038/s41467-022-30759-w.

Invariant NKT Cells Promote the Development of Highly Cytotoxic Multipotent CXCR3CCR4CD8 T Cells That Mediate Rapid Hepatocyte Allograft Rejection.

Zimmerer J, Ringwald B, Chaudhari S, Han J, Peterson C, Warren R J Immunol. 2021; 207(12):3107-3121.

PMID: 34810223 PMC: 9124232. DOI: 10.4049/jimmunol.2100334.

Critical Role of Macrophage FcγR Signaling and Reactive Oxygen Species in Alloantibody-Mediated Hepatocyte Rejection.

Zimmerer J, Liu X, Blaszczak A, Avila C, Pham T, Warren R J Immunol. 2018; 201(12):3731-3740.

PMID: 30397035 PMC: 6289737. DOI: 10.4049/jimmunol.1800333.

Activation and Regulation of B Cell Responses by Invariant Natural Killer T Cells.

Doherty D, Melo A, Moreno-Olivera A, Solomos A Front Immunol. 2018; 9:1360.

PMID: 29967611 PMC: 6015876. DOI: 10.3389/fimmu.2018.01360.

Unique CD8+ T Cell-Mediated Immune Responses Primed in the Liver.

Zimmerer J, Horne P, Fisher M, Pham T, Lunsford K, Ringwald B Transplantation. 2016; 100(9):1907-15.

PMID: 27379551 PMC: 4935926. DOI: 10.1097/TP.0000000000001290.

References

Chang P, Barral P, Fitch J, Pratama A, Ma C, Kallies A . Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses. Nat Immunol. 2011; 13(1):35-43. DOI: 10.1038/ni.2166. View

Lacha J, Hribova P, Kotsch K, Brabcova I, Bartosova K, Volk H . Effect of cytokines and chemokines (TGF-beta, TNF-alpha, IL-6, IL-10, MCP-1, RANTES) gene polymorphisms in kidney recipients on posttransplantation outcome: influence of donor-recipient match. Transplant Proc. 2005; 37(2):764-6. DOI: 10.1016/j.transproceed.2004.12.224. View

Bumgardner G, Gao D, Li J, BASKIN J, Heininger M, Orosz C . Rejection responses to allogeneic hepatocytes by reconstituted SCID mice, CD4, KO, and CD8 KO mice. Transplantation. 2001; 70(12):1771-80. DOI: 10.1097/00007890-200012270-00017. View

Coutelier J . Enhancement of IgG production elicited in mice by treatment with anti-CD8 antibody. Eur J Immunol. 1991; 21(10):2617-20. DOI: 10.1002/eji.1830211046. View

Puttarajappa C, Shapiro R, Tan H . Antibody-mediated rejection in kidney transplantation: a review. J Transplant. 2012; 2012:193724. PMC: 3337620. DOI: 10.1155/2012/193724. View

Bai L, Constantinides M, Thomas S, Reboulet R, Meng F, Koentgen F . Distinct APCs explain the cytokine bias of α-galactosylceramide variants in vivo. J Immunol. 2012; 188(7):3053-61. PMC: 3311697. DOI: 10.4049/jimmunol.1102414. View

Zimmerer J, Pham T, Wright C, Tobin K, Sanghavi P, Elzein S . Alloprimed CD8(+) T cells regulate alloantibody and eliminate alloprimed B cells through perforin- and FasL-dependent mechanisms. Am J Transplant. 2014; 14(2):295-304. PMC: 4018729. DOI: 10.1111/ajt.12565. View

Ishizaka A, Sakiyama Y, Nakanishi M, Tomizawa K, OSHIKA E, Kojima K . The inductive effect of interleukin-4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. Clin Exp Immunol. 1990; 79(3):392-6. PMC: 1534964. DOI: 10.1111/j.1365-2249.1990.tb08101.x. View

Thomas M, Noble A, Sawicka E, Askenase P, Kemeny D . CD8 T cells inhibit IgE via dendritic cell IL-12 induction that promotes Th1 T cell counter-regulation. J Immunol. 2001; 168(1):216-23. DOI: 10.4049/jimmunol.168.1.216. View

10.

Gautreaux M, Freedman B . Genotypic variation and outcomes in kidney transplantation: donor and recipient effects. Kidney Int. 2013; 84(3):431-3. PMC: 3761401. DOI: 10.1038/ki.2013.167. View

11.

Horne P, Zimmerer J, Fisher M, Lunsford K, Nadasdy G, Nadasdy T . Critical role of effector macrophages in mediating CD4-dependent alloimmune injury of transplanted liver parenchymal cells. J Immunol. 2008; 181(2):1224-31. PMC: 3022512. DOI: 10.4049/jimmunol.181.2.1224. View

12.

Tonti E, Galli G, Malzone C, Abrignani S, Casorati G, Dellabona P . NKT-cell help to B lymphocytes can occur independently of cognate interaction. Blood. 2008; 113(2):370-6. DOI: 10.1182/blood-2008-06-166249. View

13.

Ensminger S, Spriewald B, Witzke O, Morrison K, Van Maurik A, Morris P . Intragraft interleukin-4 mRNA expression after short-term CD154 blockade may trigger delayed development of transplant arteriosclerosis in the absence of CD8+ T cells. Transplantation. 2000; 70(6):955-63. DOI: 10.1097/00007890-200009270-00013. View

14.

Vilarinho S, Ogasawara K, Nishimura S, Lanier L, Baron J . Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus. Proc Natl Acad Sci U S A. 2007; 104(46):18187-92. PMC: 2084318. DOI: 10.1073/pnas.0708968104. View

15.

Ensminger S, Spriewald B, Sorensen H, Witzke O, Flashman E, Bushell A . Critical role for IL-4 in the development of transplant arteriosclerosis in the absence of CD40-CD154 costimulation. J Immunol. 2001; 167(1):532-41. DOI: 10.4049/jimmunol.167.1.532. View

16.

Horne P, Lunsford K, Walker J, Koester M, Bumgardner G . Recipient immune repertoire and engraftment site influence the immune pathway effecting acute hepatocellular allograft rejection. Cell Transplant. 2008; 17(7):829-44. DOI: 10.3727/096368908786516792. View

17.

La Cava A, Van Kaer L, Fu-Dong-Shi . CD4+CD25+ Tregs and NKT cells: regulators regulating regulators. Trends Immunol. 2006; 27(7):322-7. DOI: 10.1016/j.it.2006.05.003. View

18.

Meyer D, Schiller C, Westermann J, Izui S, Hazenbos W, Verbeek J . FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia. Blood. 1998; 92(11):3997-4002. View

19.

Brunet M, Millan O, Martorell J . Donor-recipient genetic diversity: the role of pharmacogenomics in kidney transplantation. Pharmacogenomics. 2013; 14(12):1369-72. DOI: 10.2217/pgs.13.117. View

20.

Bickerstaff A, Nozaki T, Wang J, Pelletier R, Hadley G, Nadasdy G . Acute humoral rejection of renal allografts in CCR5(-/-) recipients. Am J Transplant. 2008; 8(3):557-66. DOI: 10.1111/j.1600-6143.2007.02125.x. View