Dataset Information


Candida-elicited murine Th17 cells express high Ctla-4 compared with Th1 cells and are resistant to costimulation blockade.

ABSTRACT: Effector and memory T cells may cross-react with allogeneic Ags to mediate graft rejection. Whereas the costimulation properties of Th1 cells are well studied, relatively little is known about the costimulation requirements of microbe-elicited Th17 cells. The costimulation blocker CTLA-4 Ig has been ineffective in the treatment of several Th17-driven autoimmune diseases and is associated with severe acute rejection following renal transplantation, leading us to investigate whether Th17 cells play a role in CD28/CTLA-4 blockade-resistant alloreactivity. We established an Ag-specific model in which Th1 and Th17 cells were elicited via Mycobacterium tuberculosis and Candida albicans immunization, respectively. C. albicans immunization elicited a higher frequency of Th17 cells and conferred resistance to costimulation blockade following transplantation. Compared with the M. tuberculosis group, C. albicans-elicited Th17 cells contained a higher frequency of IL-17(+)IFN-?(+) producers and a lower frequency of IL-10(+) and IL-10(+)IL-17(+) cells. Importantly, Th17 cells differentially regulated the CD28/CTLA-4 pathway, expressing similarly high CD28 but significantly greater amounts of CTLA-4 compared with Th1 cells. Ex vivo blockade experiments demonstrated that Th17 cells are more sensitive to CTLA-4 coinhibition and therefore less susceptible to CTLA-4 Ig. These novel insights into the differential regulation of CTLA-4 coinhibition on CD4(+) T cells have implications for the immunomodulation of pathologic T cell responses during transplantation and autoimmunity.

PROVIDER: S-EPMC4071624 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC4124942 | BioStudies
2020-01-01 | S-EPMC7096747 | BioStudies
2019-01-01 | S-EPMC6658342 | BioStudies
2018-01-01 | S-EPMC5884137 | BioStudies
2012-01-01 | S-EPMC4107447 | BioStudies
1000-01-01 | S-EPMC5821191 | BioStudies
2010-01-01 | S-EPMC2915549 | BioStudies
2020-01-01 | S-EPMC7753196 | BioStudies
| S-EPMC3262878 | BioStudies
1000-01-01 | S-EPMC3198051 | BioStudies