Submitted February 8, 2002
Accepted June 3, 2002
Developmental dissociation of T cells from B, NK, and myeloid cells revealed by MHC class II-specific chimeric immune receptors bearing TCR 
- or FcR 
-chain signaling domains
WeiYu Lin and Margo R Roberts*
Corgentech Inc., Palo Alto, CA, USA
Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, University of Virginia, Charlottesville, VA, USA
* Corresponding author; email: mroberts{at}virginia.edu.
The TCR - and FcR -chains play a critical role in mediating signal transduction. We have previously described HIVgp120-specific chimeric immune receptors (CIRs) in which the extracellular domain of CD4 is linked to the signaling domain of (CD4) or (CD4). Such CIRs are efficiently expressed following retroviral transduction of mature T cells and specifically redirect effector functions toward HIV-infected targets. In this report, we examine development of CD4- or CD4-expressing T cells from retrovirally transduced hematopoietic stem cells following bone marrow transplantation (BMT). Although CD4/-expressing myeloid, NK and B cells were efficiently reconstituted, parallel development of CD4/-expressing T cells was blocked prior to the CD25+CD44+ prothymocyte stage. In contrast, T cells expressing a signaling-defective CIR were efficiently generated. When MHC class II-deficient mice were used as transplant recipients, development of CD4/-expressing T cells was restored. We conclude that CD4/-signaling generated following engagement of MHC class II selectively arrests T lineage development.
