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Preferential Priming of Alloreactive T Cells with Indirect Reactivity
Author(s) -
Brennan T. V.,
Jaigirdar A.,
Hoang V.,
Hayden T.,
Liu F.C.,
Zaid H.,
Chang C. K.,
Bucy R. P.,
Tang Q.,
Kang S.M.
Publication year - 2009
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.1600-6143.2009.02578.x
Subject(s) - priming (agriculture) , cd8 , immunology , cytotoxic t cell , t cell , transplantation , population , effector , biology , microbiology and biotechnology , immune system , medicine , in vitro , genetics , botany , germination , environmental health
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.