| abstract |
Methods are provided to specifically modulate T cell trafficking of systemic memory, in particular CD4 + T cells without affecting the T cells or T cells of intestinal memory. We show that systemic memory T cells, which are characterized as CD45RA-, and integrin a4ß7-, express high levels of CCR4. Ligands of CCR4, such as TARC or MDC, act as an adhesion trigger, where, after CCR4 binding, these cells undergo integrin-dependent arrest in the appropriate vascular receptors. This stoppage acts to locate the cells at the target site. The methods of the invention manipulate this triggering, and the chemotaxis mediated by CCR4, to affect the localization of the T cells in the target tissues. In one embodiment of the invention, the active agent is a CCR4 agonist, which acts to improve the localization of T cells. In an alternative embodiment, the agent is an antagonist that blocks the biological activity of CCR4. An advantage of the invention is the selectivity for the T cells of systemic memory, without affecting the native T cells or the T cells of intestinal memory. |