CD4(-CELLS OF BOTH THE NAIVE AND THE MEMORY PHENOTYPE ENTER RAT LYMPH-NODES AND PEYERS-PATCHES VIA HIGH ENDOTHELIAL VENULES - WITHIN THE TISSUE THEIR MIGRATORY BEHAVIOR DIFFERS() T)

It is thought that naive T cells predominantly enter lymphoid organs s uch as lymph nodes (LN) and Peyer's patches (PP) via high endothelial venules (HEV), whereas memory T cells migrate mainly into non-lymphoid organs. However, direct evidence for the existence of these distinct migration pathways in vivo is incomplete, and nothing is known about t heir migration through the different compartments of lymphoid organs. Such knowledge would be of considerable interest for understanding T c ell memory in vivo. In the present study we separated naive and memory CD4(+) T cells from the rat thoracic duct according to the expression of the high and low molecular weight isoforms of CD45R, respectively. At various time points after injection into congenic animals, these c ells were identified by quantitative immunohistology in HEV, and T and B cell areas of different LN and PP. Three major findings emerged. Fi rst, both naive and memory CD4(+) T cells enter lymphoid organs via th e HEV in comparable numbers. Second, naive and memory CD4(+) T cells m igrate into the B cell area, although in small numbers and continuousl y enter established germinal centers (GC) with a bias for memory CD4() T cells. Third, memory CD4(+) T cells migrate faster through the T c ell area of lymphoid organs than naive CD4(+) T cells. Thus, our study shows that memory CD4(+) T cells are not excluded from the HEV route. In addition, ''memory'' might depend in part on the ability of T cell s to specifically enter the B cell area and GC and to screen large qua ntities of lymphoid tissues in a short time.