Abstract
To investigate the mechanism of CD4+ T-cell help during the activation and differentiation of directly alloreactive CD8+ T cells, we examined the development of obliterative airways disease (OAD) following transplantation of airways into fully mismatched recipient mice deficient in CD4+ T cells. BALB/c trachea allografts became fibrosed significantly less frequently in B6 CD4-/- recipients as compared to wildtype controls. Furthermore, class I-directed cytotoxicity failed to develop in the absence of CD4+ T cells. The infiltration of graft tissue by primed Ld-specific directly alloreactive 2C CD8+ T cells was not found to depend on the presence of CD4+ T cells. Nevertheless, graft-infiltrating 2C CD8+ T cells failed to express CD69 and granzyme B when CD4+ T-cell help was unavailable. Importantly, reconstitution of B6 CD4-/- recipient mice with graft peptide-specific TCR-Tg CD4+ T cells (OT-II or TEa) capable of recognizing antigen only on recipient APC allowed for full expression of CD69 and granzyme B by the directly alloreactive CD8+ T cells and restored the capacity of recipients to reject their allografts. These results demonstrate that indirectly alloreactive CD4+ T cells ensure the optimal activation and differentiation of graft-infiltrating directly alloreactive CD8+ T cells independent of donor APC recognition.
Original language | English (US) |
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Pages (from-to) | 2269-2278 |
Number of pages | 10 |
Journal | American Journal of Transplantation |
Volume | 7 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2007 |
Keywords
- Allograft rejection
- Allopeptide
- T-cell differentiation
- T-cell help