Premium
New TCR Transgenic Model for Tracking Allospecific CD4 T‐Cell Activation and Tolerance in Vivo
Author(s) -
Sandner Sigrid E.,
Salama Alan D.,
Houser Stuart L.,
Palmer Ed,
Turka Laurence A.,
Sayegh Mohamed H.
Publication year - 2003
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 - 10.1046/j.1600-6143.2003.00220.x
Subject(s) - t cell receptor , t cell , adoptive cell transfer , in vivo , microbiology and biotechnology , immunology , ex vivo , il 2 receptor , effector , transplantation , biology , medicine , immune system , surgery
We have developed an adoptive transfer model system to visualize the dynamics of alloantigen‐specific CD4 + T‐cell activation in vivo . Using TCR‐transgenic (tg) mice reactive to I‐A bm12 , we studied the clonal expansion and differentiation of alloreactive T cells by tracking the fate of adoptively transferred TCR‐tg CD4 + T cells in syngeneic mice transplanted with skin grafts expressing I‐A bm12 . Following transplantation, alloantigen‐specific TCR‐tg CD4 + T‐cell expansion was observed initially in the draining lymph nodes followed by the spleen. TCR‐tg CD4 + T cells up‐regulated CD69 and CD25 expression, developed an effector/memory surface phenotype and produced IFN‐γ in response to alloantigen ex vivo . Furthermore, we validate the model system as a means for studying the effects of tolerogenic regimens on alloreactive CD4 + T cells, demonstrating that CTLA4Ig inhibits alloantigen‐dependent clonal expansion and effector function of TCR‐tg CD4 + T cells in vivo . We describe the first model for tracking alloreactive CD4 + T‐cell activation in vivo . It provides a powerful tool for studying CD4 + T‐cell mediated alloimmune responses and mechanisms of tolerance induction in vivo .