Transgenic CD4 T cells (D011.10) are destroyed in MHC-compatible hosts by NK cells and CD8 T cells

During an immune response a small number of rare Ag-specific clones proliferate extensively and decline, leaving a residual population for long-term memory. TCR transgenic (tg) CD4 T cells have been used widely to study the primary and memory response in vivo. We show here that naive TCR tg CD4 T cells from the D011.10 strain transferred into wild type (wt) BALB/c recipients and not stimulated declined rapidly at the same rate as those primed in vivo by Ag. In the same recipients wt CD4 T cells survived. There was no evidence of an inherent defect in the tg T cells, which survived well when returned to DO11.10 recipients. Surprisingly, wt CD4 T cells declined rapidly in the same DO11.10 hosts. By depleting wt recipients of NK cells or CD8(+) cells, the speed of reduction was slowed by half; rapid destruction was prevented completely by combing the two treatments. In contrast, preimmunization accelerated the loss of tg T cells. The results suggested that tg CD4 T cells were actively rejected by both NK and CD8 T cell responses. We consider whether, despite extensive backcrossing, tg T cells may retain genetic material (minor histocompatibility Ags) flanking the construct that compromises their survival in wt recipients.