Preferential priming of alloreactive T cells with indirect reactivity.
Am J Transplant
; 9(4): 709-18, 2009 Apr.
Article
in En
| MEDLINE
| ID: mdl-19344462
ABSTRACT
The relative contributions of the direct and indirect pathways in alloimmune responses have not been fully elucidated. We report a novel murine TCR transgenic system that can simultaneously track the CD4-direct (CD4-d), CD4-indirect (CD4-i) and CD8-direct (CD8-d) pathways after transplantation. Using this system, we have observed a profoundly greater proliferation of CD4-i T cells relative to CD4-d and CD8-d T cells after transplantation. Furthermore, a much larger proportion of CD4-i T cells attain an effector phenotype. We also analyzed endogenous, wild-type T cells using enzyme-linked immunospot analysis. In naïve mice, T cells with indirect reactivity were undetectable, but T cells with direct reactivity were abundant. However, 10 days after skin or heterotopic heart transplantation, CD4-i T cells comprised approximately 10% of the CD4+ response. Consistent with increased priming of the CD4-i pathway, we observed that the CD4-i T cells were further enriched in the effector cells migrating to the allograft and in memory-like T cells persisting after rejection. Thus, priming of the CD4-i pathway is favored after transplantation, allowing a rare population to rapidly become a major component of the CD4+ T-cell response in acute allograft rejection. The generalizability of this observation to other models remains to be determined.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transplantation, Homologous
/
T-Lymphocytes
/
CD4-Positive T-Lymphocytes
/
Heart Transplantation
/
Skin Transplantation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Am J Transplant
Journal subject:
TRANSPLANTE
Year:
2009
Document type:
Article
Affiliation country:
United States