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*
Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom;
National Institute for Medical Research, Division of Molecular Immunology, London, United Kingdom.
We wished to determine whether CD4+ T cells could
reject a skin graft that was discordant for a single minor
transplantation Ag in the absence of CD8+ T cells or Ab.
Transgenic A1(M) mice were constructed that express the rearranged
Vß8.2 and V
10 TCR genes from a T cell clone that is
specific for the male Ag (H-Y) in the context of H2-Ek. In
addition, the RAG-1-/- background was bred onto these
mice to eliminate any endogenous TCR rearrangements. As expected,
clonal deletion was found to be complete in the thymus of male
A1(M)xRAG-1-/- mice, while only CD4+
T cells were positively selected and found in the periphery of females.
Female A1(M)xRAG-1-/- mice were able to rapidly reject
(in <14 days) male (but not female) skin grafts in a CD4-dependent
fashion. After multiple grafts, it was confirmed that no
CD8+ T cells or surface Ig+ B cells were
present. An immunofluorescent analysis of spleen cells after grafting
showed that the majority of T cells expressed activation markers (CD44,
CD25, and intracytoplasmic IL-2) and a significant proportion were
making IFN-
and IL-4. Surprisingly, the transfer of either Th1 or
Th2 CD4+ T cell lines from these mice into T cell-depleted
recipients was sufficient to cause a specific rejection of male
skin.
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