Migration pathways of CD4 T cell subsets in vivo: the CD45RC- subset enters the thymus via α4 integrin-VCAM-1 interaction

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Abstract
The present investigation examines the localization and migration of purified T cell subsets in comparison with B cells, CD8 T cells and CD4+CD8− single-positive thymocytes. CD4 T cell subsets in the rat are defined by mAb MRC OX22 ( anti-CD45RC), which distinguishes resting CD4 T cells (CD45RC+) from those (CD45RC−) which have encountered antigen in the recent past– subpopulations often referred to as ‘naive’ and ‘memory’. Purified, 51Cr-labelled CD45RC+ CD4 T cells broadly reflected the migration pattern of CD8 T cells and B cells. Early localization to the spleen was followed by a redistribution to mesenteric lymph nodes (MLN) and cervical lymph nodes ( CLN) , B cells migrating at a slightly slower tempo. There was almost no localization of these subpopulations to the small or large intestine [Peyer's patches (PP) excluded]. In contrast, CD45RC− CD4 T cells (indistinguishable in size from 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. Numerically, localization of CD45RC− CD4 T cells in the MLN could be accounted for entirely by afferent drainage from the intestine. Unexpectedly, CD45RC− CD4 T cells (but not other subsets) localized and accumulated in the thymus. In vivo treatment with mAb HP2/1 against the integrin α4 subunit inhibited almost entirely CD45RCT− CD4 T cell migration into the PP (98.1%), intestine (87.1%) , MLN (89.1%) and thymus (93.5%) migration into the CLN was only reduced by half. To distinguish between recognition of MAdCAM-1 and VCAM-1 by α4−containing 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 completely blocked (92.3%) by anti-VCAM-1. The results indicated (i) that CD45RC− CD4 T cells alone showed enhanced localization to the gut and PP, probably via α4β7-MAdCAM-1 interaction; ( II) that many CD45RC− cells entered nonmucosal LN independently of α4 integrin or VCAM-1; and (III) that entry of mature recirculatlng CD45RC− CD4 T cells into the thymus across thymic endothellum was apparently regulated by α4 integrln-VCAM-1 interaction.

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