Intracellular adhesion molecule-1 modulates β-chemokines and directly costimulates T cells in vivo
| Autor: | Devin M. Cunning, Kesen Dang, David B. Weiner, Liesl K. Nottingham, Michael G. Agadjanyan, Ara A. Chalian, Jim Oh, Anthony Tsai, Jong J. Kim, Tzvete Dentchev, Daniel J. Lee, Lake Morrison |
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| Rok vydání: | 1999 |
| Předmět: |
Cytotoxicity
Immunologic Immunogen T-Lymphocytes Intercellular Adhesion Molecule-1 Vascular Cell Adhesion Molecule-1 chemical and pharmacologic phenomena Biology Lymphocyte Activation Article Interferon-gamma Mice Adjuvants Immunologic Antigens CD Vaccines DNA Animals Humans Cytotoxic T cell Chemokine CCL4 Cell adhesion Chemokine CCL3 AIDS Vaccines CD86 Mice Inbred BALB C Membrane Glycoproteins Cell adhesion molecule CD28 T-Lymphocytes Helper-Inducer General Medicine Macrophage Inflammatory Proteins CD58 Antigens Intercellular adhesion molecule Molecular biology Recombinant Proteins Fusion Proteins gag-pol B7-1 Antigen HIV-1 Female B7-2 Antigen |
| Zdroj: | Journal of Clinical Investigation. 103:869-877 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci6024 |
| Popis: | The potential roles of adhesion molecules in the expansion of T cell-mediated immune responses in the periphery were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the adhesion molecules intracellular adhesion molecule-1 (ICAM-1), lymphocyte function associated-3 (LFA-3), and vascular cell adhesion molecule-1 (VCAM-1) along with DNA immunogens, and we analyzed the resulting antigen-specific 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 proliferative responses. In addition, coimmunization with pCICAM-1 (and more moderately with pCLFA-3) resulted in a dramatic enhancement of CD8-restricted cytotoxic T-lymphocyte responses. Although VCAM-1 and ICAM-1 are similar in size, VCAM-1 coimmunization did not have any measurable effect on cell-mediated 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-1alpha (MIP-1alpha), MIP-1beta, and regulated on activation normal T-cell expression and secreted (RANTES) produced by stimulated T cells. Through comparative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathways are independent of CD86/CD28 pathways and that they may synergistically expand T-cell responses in vivo. |
| Databáze: | OpenAIRE |
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