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| B7 BUT NOT INTERCELLULAR-ADHESION MOLECULE-1 COSTIMULATION PREVENTS THE INDUCTION OF HUMAN ALLOANTIGEN-SPECIFIC TOLERANCE |
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| Author(s): BOUSSIOTIS VA, FREEMAN GJ, GRAY G, GRIBBEN J, NADLER LM |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 178 Issue: 5 Pages: 1753-1763 Published: NOV 1 1993 |
| Times Cited: 210 References: 48 |
| Abstract: Presentation of antigen by the major histocompatibility complex to T lymphocytes without the requisite costimulatory signals does not induce an immune response but rather results in a state of antigen-specific unresponsiveness, termed anergy. To determine which costimulatory signals are critical for the T cell commitment to activation or anergy, we developed an in vitro model system that isolated the contributions of alloantigen and each candidate costimulatory molecule. Here, we show that transfectants expressing HLA-DR7 and either B7 or intercellular adhesion molecule 1 (ICAM-1) deliver independent costimulatory signals resulting in alloantigen-induced proliferation of CD4-positive T lymphocytes. Although equivalent in their ability to costimulate maximal proliferation of alloreactive T cells, B7 but not ICAM-1 induced detectable interleukin 2 secretion and prevented the induction of alloantigen-specific anergy. These results are consistent with the hypothesis that blockade of the ICAM-1:lymphocyte function-associated 1 pathway results in immunosuppression, whereas blockade of the B7:CD28/CTLA4 pathway results in alloantigen-specific anergy. This approach, using this model system, should facilitate the identification of critical costimulatory pathways which must be inhibited in order to induce alloantigen-specific tolerance before human organ transplantation. |
| Document Type: Article |
| Language: English |
| Reprint Address: BOUSSIOTIS, VA (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, MAYER 730, 44 BINNEY ST, BOSTON, MA 02115 USA |
Addresses:
1. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA
2. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA
3. REPLIGEN INC, CAMBRIDGE, MA 02139 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: MD953 |
| ISSN: 0022-1007 |
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