Vector-driven hyperexpression of a triad of costimulatory molecules confers enhanced T-cell stimulatory capacity to DC precursors

Activation of T cells requires at least two signals: signal 1, via the T-ce ll receptor, and signal 2, in which a costimulatory molecule on the antigen presenting cell (APC) interacts with a ligand on the T cell. Dendritic cel ls (DCs) are the most potent APCs in part due to their expression of costim ulatory molecules. DCs, however, constitute only a minor percentage of APCs in the body, and the in vitro preparation of DCs is both costly and time c onsuming. The studies reported here demonstrate that one can utilize other APCs, such as bone marrow progenitor cells (BMPCs) and make them markedly m ore effective as APCs; this was accomplished by their infection with recomb inant poxviruses (either the replication-defective avipox or vaccinial, whi ch contain transgenes for a triad of costimulatory molecules (B7-1, ICAM-1 and LFA-3, designated TRICOM). APCs infected with TRICOM vectors are shown to significantly enhance the activation of both naive and effector CD4(+) a nd CD8(+) T-cell populations. The use of TRICOM vectors in vaccine strategi es is discussed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .