MIGRATION PATHWAYS OF CD4 T-CELL SUBSETS IN-VIVO - THE CD45RC(-) SUBSET ENTERS THE THYMUS VIA ALPHA(4) INTEGRIN-VCAM-1 INTERACTION

The present investigation examines the localization and migration of p urified T cell subsets in comparison with B cells, CD8 T cells and CD4 (+)CD8(-) single-positive thymocytes, CD4 T cell subsets in the rat ar e defined by mAb MRC OX22 (anti-CD45RC), which distinguishes resting C D4 T cells (CD45RC(+)) from those (CD45RC(-)) which have encountered a ntigen in the recent past-subpopulations often referred to as 'naive' and 'memory', Purified, Cr-51-labelled CD45RC(+) CD4 T cells broadly r eflected the migration pattern of CD8 T cells and B cells, Early local ization to the spleen was followed by a redistribution to mesenteric l ymph nodes (MLN) and cervical lymph nodes (CLN), B cells migrating at a slightly slower tempo, There was almost no localization of these sub populations to the small or large intestine [Peyer's patches (PP) excl uded], In contrast, CD45RC(-) CD4 T cells (indistinguishable in size f rom the CD45RC(+) subset) localized in large numbers to the intestine; they were present here at the earliest time point (0.5 h), persisted for at least 48 h but did not accumulate, indicating a rapid exit, Num erically, localization of CD45RC(-) CD4 T cells in the MLN could be ac counted for entirely by afferent drainage from the intestine, Unexpect edly, CD45RC(-) CD4 T cells (but not other subsets) localized and accu mulated in the thymus, In vivo treatment with mAb HP2/1 against the in tegrin alpha(4) subunit inhibited almost entirely CD45RC(-) CD4 T cell migration into the PP (98.1%), intestine (87.1%), MLN (89.1%) and thy mus (93.5%); migration into the CLN was only reduced by half, To disti nguish between recognition of MAdCAM-1 and VCAM-1 by alpha(4)-containi ng integrins, recipients were treated with mAb 5F10 against rat VCAM-1 , Except for the thymus and a small reduction in CLN, localization of CD45RC(-) CD4 T cells was unaffected; entry to the thymus was almost c ompletely blocked (92.3%) by anti-VCAM-1. The results indicated (i) th at CD45RC(-) CD4 T cells alone showed enhanced localization to the gut and PP probably via alpha(4) beta(7)-MAdCAM-1 interaction; (ii) that many CD45RC(-) cells entered non-mucosal LN independently of alpha(4) integrin or VCAM-1; and (iii) that entry of mature recirculating CD45R C(-) CD4 T cells into the thymus across thymic endothelium was apparen tly regulated by alpha(4) integrin-VCAM-1 interaction.