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Allopeptide‐Specific CD4 + T Cells Facilitate the Differentiation of Directly Alloreactive Graft‐Infiltrating CD8 + T Cells
Author(s) -
Richards D. M.,
Zhang N.,
Dalheimer S. L.,
Mueller D. L.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.01934.x
Subject(s) - cytotoxic t cell , medicine , cd8 , immunology , microbiology and biotechnology , immune system , biology , genetics , in vitro
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 L d ‐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.