Lymphocyte migration into cell-mediated immune lesions is inhibited by trypsin

Abstract

THE lymph nodes and the white pulp of the spleen are major sites into which lymphocytes migrate from the blood and each organ is equally selective in that other blood cells are efficiently excluded^1,2. It might be expected that the same mechanism for discriminating between lymphocytes and other cells would have evolved in the spleen and lymph nodes, but the entry of lymphocytes into each of these organs can be distinguished in two ways. First, the histological appearance of the vascular endothelium across which lymphocytes migrate is dissimilar^1,3 and second, the capacity of lymphocytes to migrate from the blood into lymph nodes is reduced by brief exposure in vitro to low concentrations of trypsin, but migration of the same population into the spleen is barely affected⁴. Lymphoctyes are not irreversibly damaged by trypsin because they regain their capacity both in vivo and in vitro⁵ to localise in lymph nodes. The reduced numbers in lymph nodes is not a consequence of increased localisation of trypsinised lymphocytes elsewhere, as is testified by perfusing trypsinised lymphocytes through an isolated lymph node⁶ and also by measuring the numbers of trypsinised lymphocytes in the blood after intravenous injection^6,7. For several hours the concentration of treated cells in the blood was about 1.4 times that of control cells. This excess was attributed to the failure of trypsinised cells to enter lymph nodes⁶. We have extended these observations by comparing the capacity of trypsinised and control lymphocytes to migrate from the blood into several non-lymphoid tissues including sites of inflammation. Exposure of lymphocytes to trypsin not only exerts a differential effect on lymph node and spleen localisation, it also differentiates the mechanism by which lymphocytes migrate in small numbers into normal skin and other non-lymphoid tissues (trypsin resistant) from that responsible for the migration of increased numbers of lymphocytes into cell-mediated immune (CMI) lesions in the skin (trypsin sensitive).