ANTIBODIES TO LYMPHOTOXIN-ALPHA (LT-ALPHA) AND LT-BETA RECOGNIZE DIFFERENT GLIAL-CELL TYPES IN THE CENTRAL-NERVOUS-SYSTEM

The cytokine lymphotoxin (LT) is known to exist in two forms, secreted LT alpha and a membrane-bound LT alpha/beta complex. LT alpha shares the same receptor as tumor necrosis factor alpha and LT beta is recogn ized by its receptor, LT beta R. Since LT has been associated with oli godendrocyte pathology, the present study has examined the expression of these molecules by immunocytochemistry in diseased and normal CNS t issue, with a panel of monoclonal antibodies (mAb) to LT alpha, LT bet a and LT beta R. Of three mAb to LT beta, two (B27 and C37) gave speci fic membrane staining on astrocytes, as well as lymphocytes. The third anti-LT beta mAb, B9, was selectively immunoreactive for oligodendroc ytes, suggesting specific recognition sites. The reactivity was not sp ecific for multiple sclerosis (MS) since oligodendrocytes in normal an d non-MS CNS tissue also displayed positivity. MAb to LT beta R reacte d with astrocytes only, giving a punctate membrane staining pattern su ggestive of receptor sites. MAb to LT alpha gave strong reactivity on lymphocytes in active MS lesions and weak reactivity on microglia with in lesion areas. These results show that mAb to LT alpha and LT beta r ecognize different cell types within the CNS. Furthermore, individual mAb against LT beta were capable of distinguishing between astrocytes and oligodendrocytes, perhaps indicative of different epitopes on LT b eta. The presence of LT beta R on astrocytes suggests possible interac tions between infiltrating lymphocytes and astrocytes via the LT pathw ay. (C) 1997 Elsevier Science B.V.