| Autor: |
Abdi, Reza, Smith, R. Neal, Makhlouf, Leila, Najafian, Nader, Luster, Andrew D., Auchincloss Jr., Hugh, Sayegh, Mohamed H. |
| Předmět: |
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| Zdroj: |
Diabetes; Aug2002, Vol. 51 Issue 8, p2480, 16p, 2 Black and White Photographs, 4 Graphs |
| Abstrakt: |
Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4[sup +] T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotocin-induced diabetic mouse model. BALB/c islet allografts transplanted into CCR5[sup -/-] (C57BL/6) recipients survived significantly longer (mean survival time, 38 ± 8 days) compared with those transplanted into wild-type control mice (10 ± 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5[sup -/-] animals without other treatment survived >90 days. In CCR5[sup -/-] mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon-γ was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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