Thalidomide with Blockade of Co-stimulatory Molecules Prolongs the Survival of Alloantigen-primed Mice with Cardiac Allografts

Overview

Journal BMC Immunol

Publisher Biomed Central

Specialty Allergy & Immunology

Date 2020 Apr 18

PMID 32299357

Citations 2

Authors

Maoshu Zhu

Yunhan Ma

Kai Tan

Liyi Zhang

Zhaowei Wang

Yongsheng Li

Yingyu Chen

Junjun Guo

Guoliang Yan

Zhongquan Qi

Affiliations

Soon will be listed here.

Abstract

Background: Miscellaneous memory cell populations that exist before organ transplantation are crucial barriers to transplantation. In the present study, we used a skin-primed heart transplantation model in mouse to evaluate the abilities of Thalidomide (TD), alone or in combination with co-stimulatory blockade, using monoclonal antibodies (mAbs) against memory T cells and alloantibodies to prolong the second cardiac survival.

Results: In the skin-primed heart transplantation model, TD combined with mAbs significantly prolonged the second cardiac survival, accompanied by inhibition of memory CD8 T cells. This combined treatment enhanced the CD4Foxp3 regulatory T cells ratio in the spleen, restrained the infiltration of lymphocytes into the allograft, and suppressed the allo-response of spleen T cells in the recipient. The levels of allo-antibodies also decreased in the recipient serum. In addition, we detected low levels of the constitutions of the lytic machinery of cytotoxic cells, which cause allograft damage.

Conclusions: Our study indicated a potential synergistic action of TD in combination with with mAbs to suppress the function of memory T cells and increase the survival of second allografts in alloantigen-primed mice.

Citing Articles

Correction: Thalidomide with blockade of costimulatory molecules prolongs the survival of alloantigen-primed mice with cardiac allografts.

Zhu M, Ma Y, Tan K, Zhang L, Wang Z, Li Y BMC Immunol. 2022; 23(1):38.

PMID: 35945504 PMC: 9361527. DOI: 10.1186/s12865-022-00512-5.

Berberine Prolongs Mouse Heart Allograft Survival by Activating T Cell Apoptosis the Mitochondrial Pathway.

Ma Y, Yan G, Guo J, Li F, Zheng H, Wang C Front Immunol. 2021; 12:616074.

PMID: 33732240 PMC: 7959711. DOI: 10.3389/fimmu.2021.616074.

References

McFarland R, Douek D, Koup R, Picker L . Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci U S A. 2000; 97(8):4215-20. PMC: 18202. DOI: 10.1073/pnas.070061597. View

Sanz I, Wei C, Lee F, Anolik J . Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol. 2008; 20(1):67-82. PMC: 2440717. DOI: 10.1016/j.smim.2007.12.006. View

Dhanda R, Shah Y, Bardapure M, Bhattacharjya S, Sharma A . Excellent renal allograft survival in donor-specific antibody transplant patients--role of intravenous immunoglobulin and rabbit antithymocyte globulin. Transplantation. 2009; 88(3):444. DOI: 10.1097/TP.0b013e3181af3914. View

Sprent J, Surh C . T cell memory. Annu Rev Immunol. 2002; 20:551-79. DOI: 10.1146/annurev.immunol.20.100101.151926. View

Kaech S, Wherry E, Ahmed R . Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol. 2002; 2(4):251-62. DOI: 10.1038/nri778. View

Zhang Q, Chen Y, Fairchild R, Heeger P, Valujskikh A . Lymphoid sequestration of alloreactive memory CD4 T cells promotes cardiac allograft survival. J Immunol. 2006; 176(2):770-7. DOI: 10.4049/jimmunol.176.2.770. View

Chen Y, Heeger P, Valujskikh A . In vivo helper functions of alloreactive memory CD4+ T cells remain intact despite donor-specific transfusion and anti-CD40 ligand therapy. J Immunol. 2004; 172(9):5456-66. DOI: 10.4049/jimmunol.172.9.5456. View

Wang Y, Li D, Nurieva R, Yang J, Sen M, Carreno R . LFA-1 affinity regulation is necessary for the activation and proliferation of naive T cells. J Biol Chem. 2009; 284(19):12645-53. PMC: 2675993. DOI: 10.1074/jbc.M807207200. View

Li D, Molldrem J, Ma Q . LFA-1 regulates CD8+ T cell activation via T cell receptor-mediated and LFA-1-mediated Erk1/2 signal pathways. J Biol Chem. 2009; 284(31):21001-10. PMC: 2742865. DOI: 10.1074/jbc.M109.002865. View

10.

Nicolls M, Coulombe M, Beilke J, Gelhaus H, Gill R . CD4-dependent generation of dominant transplantation tolerance induced by simultaneous perturbation of CD154 and LFA-1 pathways. J Immunol. 2002; 169(9):4831-9. DOI: 10.4049/jimmunol.169.9.4831. View

11.

Corbascio M, Mahanty H, Osterholm C, Qi Z, Pearson T, Larsen C . Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice. Transplantation. 2002; 74(1):35-41. DOI: 10.1097/00007890-200207150-00007. View

12.

Metzler B, Gfeller P, Bigaud M, Li J, Wieczorek G, Heusser C . Combinations of anti-LFA-1, everolimus, anti-CD40 ligand, and allogeneic bone marrow induce central transplantation tolerance through hemopoietic chimerism, including protection from chronic heart allograft rejection. J Immunol. 2004; 173(11):7025-36. DOI: 10.4049/jimmunol.173.11.7025. View

13.

Nicolls M, Coulombe M, Yang H, Bolwerk A, Gill R . Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4. J Immunol. 2000; 164(7):3627-34. DOI: 10.4049/jimmunol.164.7.3627. View

14.

Zhai Y, Meng L, Gao F, Busuttil R, Kupiec-Weglinski J . Allograft rejection by primed/memory CD8+ T cells is CD154 blockade resistant: therapeutic implications for sensitized transplant recipients. J Immunol. 2002; 169(8):4667-73. DOI: 10.4049/jimmunol.169.8.4667. View

15.

Valujskikh A, Li X . Frontiers in nephrology: T cell memory as a barrier to transplant tolerance. J Am Soc Nephrol. 2007; 18(8):2252-61. DOI: 10.1681/ASN.2007020151. View

16.

Adams A, Williams M, Jones T, Shirasugi N, Durham M, Kaech S . Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest. 2003; 111(12):1887-95. PMC: 161424. DOI: 10.1172/JCI17477. View

17.

Lenz W . A short history of thalidomide embryopathy. Teratology. 1988; 38(3):203-15. DOI: 10.1002/tera.1420380303. View

18.

Teo S, Resztak K, Scheffler M, Kook K, Zeldis J, Stirling D . Thalidomide in the treatment of leprosy. Microbes Infect. 2002; 4(11):1193-202. DOI: 10.1016/s1286-4579(02)01645-3. View

19.

Tamura F, Vogelsang G, Reitz B, Baumgartner W, Herskowitz A . Combination thalidomide and cyclosporine for cardiac allograft rejection. Comparison with combination methylprednisolone and cyclosporine. Transplantation. 1990; 49(1):20-5. DOI: 10.1097/00007890-199001000-00005. View

20.

Hellmann K, DUKE D, TUCKER D . PROLONGATION OF SKIN HOMOGRAFT SURVIVAL BY THALIDOMIDE. Br Med J. 1965; 2(5463):687-9. PMC: 1846106. DOI: 10.1136/bmj.2.5463.687. View