T-cell activation, proliferation, and memory after cardiac transplantation in vivo.
OBJECTIVE
To study the response of alloantigen (H2Kb)-specific T cells to a H2b+ cardiac allograft in vivo.


BACKGROUND
The response of T cells to alloantigen has been well characterized in vitro but has proved more difficult to assess in vivo. The aim of these experiments was to develop a model of T-cell-mediated rejection where the response of T cells after transplantation of a cardiac allograft could be followed in vivo.


METHODS
Purified CD8+ T cells from H2Kb-specific TCR transgenic mice (BM3; H2k) were adoptively transferred into thymectomized, T-cell-depleted CBA/Ca (H2k) mice. These mice were then transplanted with a H2Kb+ cardiac allograft. Using four-color flow cytometry, the proliferative response, modulation of activation markers, and potential cytokine production of the H2Kb-specific T cells was assessed after transplantation.


RESULTS
Consistent rejection of H2Kb+ cardiac allografts required the transfer of at least 6 x 10(6) CD8+ H2Kb-specific T cells. Short-term analyses revealed that the transgenic-TCR+/ CD8+ T cells proliferated and became activated after transplantation of an H2Kb+ cardiac allograft. Fifty days after transplantation, the transgenic-TCR+/CD8+ T cells remained readily detectable, bore a predominantly memory phenotype (CD44hi), and rapidly produced interleukin 2 and interferon-gamma on in vitro restimulation.


CONCLUSIONS
These data show that the activation of alloantigen-specific T cells can be followed in vivo in short-term and long-term experiments, thereby providing a unique opportunity to study the mechanisms by which T cells respond to allografts in vivo.
Jones
N D
ND
Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, United Kingdom.
Van Maurik
A
A
Hara
M
M
Gilot
B J
BJ
Morris
P J
PJ
Wood
K J
KJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002455:Cell Division; D016027:Heart Transplantation / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell