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Functional Characteristics and Phenotypic Plasticity of CD57+PD1- CD4 T Cells and Their Relationship with Transplant Immunosuppression.

Publication ,  Journal Article
Shaw, BI; Espinosa, JR; Stempora, L; Miller, A; Adams, B; Kirk, AD
Published in: J Immunol
April 1, 2021

Costimulation blockade (CoB)-based immunosuppression offers the promise of improved transplantation outcomes with reduced drug toxicity. However, it is hampered by early acute rejections, mediated at least in part by differentiated, CoB-resistant T cells, such as CD57+PD1- CD4 T cells. In this study, we characterize these cells pretransplant, determine their fate posttransplant, and examine their proliferative capacity in vitro in humans. Our studies show that CD57+PD1- CD4 T cells are correlated with increasing age and CMV infection pretransplant, and persist for up to 1 y posttransplant. These cells are replication incompetent alone but proliferated in the presence of unsorted PBMCs in a contact-independent manner. When stimulated, cells sorted by CD57/PD1 status upregulate markers of activation with proliferation. Up to 85% of CD57+PD1- cells change expression of CD57/PD1 with stimulation, typically, upregulating PD1 and downregulating CD57. PD1 upregulation is accentuated in the presence of rapamycin but prevented by tacrolimus. These data support a general theory of CoB-resistant cells as Ag-experienced, costimulation-independent cells and suggest a mechanism for the synergy of belatacept and rapamycin, with increased expression of the activation marker PD1 potentiating exhaustion of CoB-resistant cells.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2021

Volume

206

Issue

7

Start / End Page

1668 / 1676

Location

United States

Related Subject Headings

  • Tacrolimus
  • Sirolimus
  • Programmed Cell Death 1 Receptor
  • Phenotype
  • Middle Aged
  • Male
  • Kidney Transplantation
  • Kidney Failure, Chronic
  • Immunosuppressive Agents
  • Immunosuppression Therapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shaw, B. I., Espinosa, J. R., Stempora, L., Miller, A., Adams, B., & Kirk, A. D. (2021). Functional Characteristics and Phenotypic Plasticity of CD57+PD1- CD4 T Cells and Their Relationship with Transplant Immunosuppression. J Immunol, 206(7), 1668–1676. https://doi.org/10.4049/jimmunol.2000736
Shaw, Brian I., Jaclyn R. Espinosa, Linda Stempora, Allison Miller, Bartley Adams, and Allan D. Kirk. “Functional Characteristics and Phenotypic Plasticity of CD57+PD1- CD4 T Cells and Their Relationship with Transplant Immunosuppression.J Immunol 206, no. 7 (April 1, 2021): 1668–76. https://doi.org/10.4049/jimmunol.2000736.
Shaw BI, Espinosa JR, Stempora L, Miller A, Adams B, Kirk AD. Functional Characteristics and Phenotypic Plasticity of CD57+PD1- CD4 T Cells and Their Relationship with Transplant Immunosuppression. J Immunol. 2021 Apr 1;206(7):1668–76.
Shaw, Brian I., et al. “Functional Characteristics and Phenotypic Plasticity of CD57+PD1- CD4 T Cells and Their Relationship with Transplant Immunosuppression.J Immunol, vol. 206, no. 7, Apr. 2021, pp. 1668–76. Pubmed, doi:10.4049/jimmunol.2000736.
Shaw BI, Espinosa JR, Stempora L, Miller A, Adams B, Kirk AD. Functional Characteristics and Phenotypic Plasticity of CD57+PD1- CD4 T Cells and Their Relationship with Transplant Immunosuppression. J Immunol. 2021 Apr 1;206(7):1668–1676.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2021

Volume

206

Issue

7

Start / End Page

1668 / 1676

Location

United States

Related Subject Headings

  • Tacrolimus
  • Sirolimus
  • Programmed Cell Death 1 Receptor
  • Phenotype
  • Middle Aged
  • Male
  • Kidney Transplantation
  • Kidney Failure, Chronic
  • Immunosuppressive Agents
  • Immunosuppression Therapy