In Vivo Studies of Rantes and the Recruitment of Lymphocytes to Inflammatory Sites

Abstract

The inflamed human appendix has been demonstrated to specifically recruit CD45RO+ve T lymphocytes from the peripheral circulation; lymphocytes with the CD45RA+ve phenotype are drained from the appendix in efferent lymphatics. This recruitment has been demonstrated to change the functional repertoire of the lymphocyte population in the appendix when tested in proliferation assays, with responses to recall antigen demonstrable in lymphocytes from inflamed, but not normal appendices. Increased expression of adhesion molecules in the tissue, or soluble molecules in the circulation has not been measurable in all inflamed appendices, and may therefore not completely explain this selectivity. We observed increased expression of Rantes peptide in the areas of inflamed appendix, and around the efferent lymphatics. There was minimal staining in normal appendices, restricted to the germinal centres. Facs analysis of appendiceal and peripheral lymphocytes showed Rantes positivity to be predominantly on the CD3+ve, CD4+ve CD45RO+ve population. Using a single cell secretion assay to test lymphocytes activated in vitro, we observed Rantes secretion by T lymphocytes activated by mitogen, CD3 and CD2. The frequency of secreting lymphocytes was increased by activating with costimuli such as CD28. We suggest the thesis that Rantes secretion by T lymphocytes is a significant component in the active recruitment of a CD45RO+ve lymphocyte population to the inflamed human appendix. This mechanism may be a general feature of inflammatory recruitment in vivo.