| First Author | Brennan TV | Year | 2009 |
| Journal | Am J Transplant | Volume | 9 |
| Issue | 4 | Pages | 709-18 |
| PubMed ID | 19344462 | Mgi Jnum | J:278587 |
| Mgi Id | MGI:6359137 | Doi | 10.1111/j.1600-6143.2009.02578.x |
| Citation | Brennan TV, et al. (2009) Preferential priming of alloreactive T cells with indirect reactivity. Am J Transplant 9(4):709-18 |
| abstractText | 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 naive 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. |
