Submitted October 31, 2002
Accepted January 31, 2003
Signaling through MHC in transgenic mice generates a population of memory phenotype cytolytic cells that lack TCR
Hugh I McFarland*, Susan A Hansal, Diane I Morris, Daniel W McVicar, Paul E Love, and Amy S Rosenberg
Laboratory of Immunology, Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
* Corresponding author; email: McFarlandh{at}cber.fda.gov.
We constructed a chimeric molecule, composed of the T cell receptor (TCR)-
chain fused to the extracellular domains of a prototypical allogeneic major histocompatibility complex (MHC) class I molecule, Dd, to assess whether such a construct could impact on Dd allospecific responses in vitro and in vivo. To generate cytotoxic T lymphocytes(CTL) expressing the construct, Dd- was targeted to lymphocyte populations in transgenic mice by placing its expression under control of the CD2 promoter. In response to ligation of Dd, lymphocytes from transgenic mice expressing high levels of Dd- are activated to proliferate and kill cells binding to Dd, despite the near total loss of CD8+ T cells in these mice. Thus, the Dd- cytolytic cell was found not to be a conventional CD8+ CTL, but rather an unusual T lineage cell (CD3-CD5+Thy1.1+ ) that lacked 
or 
TCR, as well as CD4 and CD8 co-receptors, but expressed surface markers strikingly similar to memory CTL, including CD44, Ly-6C and CD122. These cells originate in the thymus and potently veto responses to Dd in vitro. Lacking TCR, these veto cells are unlikely to mediate graft versus host disease (GVHD) and thus may be useful as a cellular therapy for therapeutic deletion of alloreactive T cells in the settings of graft rejection and GVHD.
