LYMPHOCYTES INFILTRATING THE CNS DURING INFLAMMATION DISPLAY A DISTINCTIVE PHENOTYPE AND BIND TO VCAM-1 BUT NOT TO MADCAM-1

The nature of inflammatory lymphocytes recruited to the CNS has been studied in a model of chronic inflammation, Injection of killed Corynebacterium parvum into the cortex of the mouse brain produces a circumscribed inflammatory cellular infiltrate around the injection site, and recruited mononuclear inflammatory cells (IC) can be isolated for flow cytometric analysis, The majority of IC were T cells, In comparison with the predominant naive population of mesenteric lymph node T cells, IC T cells express much higher levels of CD44, LFA-1 and ICAM-1, and lower levels of CD45RB, features commonly associated with memory (previously activated) cells, In addition, in contrast to the L-selectin(+) alpha 6-integrin(low) phenotype of naive lymph node T cells, IC T cells lacked L-selectin and were alpha 6-integrin(-). Mac-1, recently proposed as another marker of memory T cell differentation, was not displayed by IC T cells, suggesting that Mac-1 expression may be heterogeneous among memory T cell subsets, A subset of mesenteric lymph node (MLN)T cells, probably representing activated T cells undergoing the naive to memory transition, but not of IC T cells, expressed high levels of alpha 6-, beta 7- and alpha E-integrin, IC and MLN naive T cells expressed comparable levels of alpha 4-integrin, but IC T cells stain poorly with anti-beta 7 mAbs and with mAb DATK 32, specific for the alpha 4 beta 7 heterodimeric lymphocyte homing receptor for the mucosal addressin MAdCAM-1, suggesting that these inflammatory cells express more alpha 4 beta 1 than alpha 4 beta 7. Consistent with this, in in vitro adhesion assays, brain IC bound better than MLN cells to the alpha 4 beta 1 integrin ligand VCAM-1 and the LFA-1 ligand ICAM-1 but adhered very poorly to the alpha 4 beta 7 ligand MAdCAM-1, These findings are consistent with and extend previous immunohistological studies of T cells in murine experimental autoimmune encephalomyelitis, and demonstrate a distinctive phenotype for lymphocytes being present in the chronically inflamed brain.