Blood, 15 October 2002, Vol. 100, No. 8, pp. 3045-3048
BRIEF REPORT
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
Wei Yu Lin and
Margo R. Roberts
From the University of Virginia,
Charlottesville.
The T-cell receptor 
(TCR-) and FcR-
chains
play a critical role in mediating signal transduction. We have
previously described HIV glycoprotein 120 (gp120)-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. 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 major
histocompatibility complex (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.
