Intracellular adhesion molecule-1 modulates beta-chemokines and directly costimulates T cells in vivo

The potential roles of adhesion molecules in the expansion of T cell-mediat ed immune responses in the periphery were examined using DNA immunogen cons tructs as model antigens. We coimmunized cDNA expression cassettes encoding the adhesion molecules intracellular adhesion molecule-1 (ICAM-1), lymphoc yte function associated-3 (LFA-3), and vascular cell adhesion molecule-1 (V CAM-1) along with DNA immunogens, and we analyzed the resulting antigen-spe cific immune responses. We observed that antigen-specific T-cell responses can be enhanced by the coexpression of DNA immunogen and adhesion molecules ICAM-1 and LFA-3. Coexpression of ICAM-1 or LFA-3 molecules along with DNA immunogens resulted in a significant enhancement of T-helper cell prolifer ative responses. In addition, coimmunization with pCICAM-1 (and more modera tely with pCLFA-3) resulted in a dramatic enhancement of CD8-restricted cyt otoxic T-lymphocyte responses. Although VCAM-1 and ICAM-1 are similar in si ze, VCAM-1 coimmunization did not have any measurable effect on cell-mediat ed responses. These results suggest that ICAM-1 and LFA-3 provide direct T- cell costimulation. These observations are further supported by the finding that coinjection with ICAM-1 dramatically enhanced the level of interferon -gamma (IFN-gamma) and beta-chemokines macrophage inflammatory protein-1 al pha (MIP-1 alpha), MIP-1 beta, and regulated on activation normal T-cell ex pression and secreted (RANTES) produced by stimulated T cells. Through comp arative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathway s are independent of CD86/CD28 pathways and that they may synergistically e xpand T-cell responses in vivo.