TY - JOUR
T1 - Antibodies to lymphotoxin α (LTα) and LTβ recognize different glial cell types in the central nervous system
AU - Cannella, Barbara
AU - Dougas Sizing, Irene
AU - Benjamin, Christopher D.
AU - Browning, Jeffrey L.
AU - Raine, Cedric S.
N1 - Funding Information:
We thank Dr. Celia Brosnan (Albert Einstein College of Medicine) for helpful discussion; Everett Swanson for technical assistance and Cenk Sumen, Konrad Miatkowski and Joe Amatucci for the purification of the mAb. Supported in part by HHS grants NS 08952, NS 11920 and NS 07098 and grant RG 1001-I-9 from the National Multiple Sclerosis Society.
PY - 1997/9
Y1 - 1997/9
N2 - The cytokine lymphotoxin (LT) is known to exist in two forms, secreted LTα and a membrane-bound LTα/β complex. LTα shares the same receptor as tumor necrosis factor a and LTβ is recognized by its receptor, LTβR. Since LT has been associated with oligodendrocyte pathology, the present study has examined the expression of these molecules by immunocytochemistry in diseased and normal CNS tissue, with a panel of monoclonal antibodies (mAb) to LTα, LTβ and LTβR. Of three mAb to LTβ, two (B27 and c37) gave specific membrane staining on astrocytes, as well as lymphocytes. The third anti-LTβ mAb, B9, was selectively immunoreactive for oligodendrocytes, suggesting specific recognition sites. The reactivity was not specific for multiple sclerosis (MS) since oligodendrocytes in normal and non-MS CNS tissue also displayed positivity. MAb to LTβR reacted with astrocytes only, giving a punctate membrane staining pattern suggestive of receptor sites. MAb to LTβ gave strong reactivity on lymphocytes in active MS lesions and weak reactivity on microglia within lesion areas. These results show that mAb to LTα and LTβ recognize different cell types within the CNS. Furthermore, individual mAb against LTβ were capable of distinguishing between astrocytes and oligodendrocytes, perhaps indicative of different epitopes on LTβ. The presence of LTβR on astrocytes suggests possible interactions between infiltrating lymphocytes and astrocytes via the LT pathway.
AB - The cytokine lymphotoxin (LT) is known to exist in two forms, secreted LTα and a membrane-bound LTα/β complex. LTα shares the same receptor as tumor necrosis factor a and LTβ is recognized by its receptor, LTβR. Since LT has been associated with oligodendrocyte pathology, the present study has examined the expression of these molecules by immunocytochemistry in diseased and normal CNS tissue, with a panel of monoclonal antibodies (mAb) to LTα, LTβ and LTβR. Of three mAb to LTβ, two (B27 and c37) gave specific membrane staining on astrocytes, as well as lymphocytes. The third anti-LTβ mAb, B9, was selectively immunoreactive for oligodendrocytes, suggesting specific recognition sites. The reactivity was not specific for multiple sclerosis (MS) since oligodendrocytes in normal and non-MS CNS tissue also displayed positivity. MAb to LTβR reacted with astrocytes only, giving a punctate membrane staining pattern suggestive of receptor sites. MAb to LTβ gave strong reactivity on lymphocytes in active MS lesions and weak reactivity on microglia within lesion areas. These results show that mAb to LTα and LTβ recognize different cell types within the CNS. Furthermore, individual mAb against LTβ were capable of distinguishing between astrocytes and oligodendrocytes, perhaps indicative of different epitopes on LTβ. The presence of LTβR on astrocytes suggests possible interactions between infiltrating lymphocytes and astrocytes via the LT pathway.
KW - Astrocytes
KW - Central nervous system
KW - Immunocytochemistry
KW - Lymphotoxin
KW - Multiple sclerosis
KW - Oligodendrocytes
UR - http://www.scopus.com/inward/record.url?scp=0342618656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0342618656&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(97)00098-2
DO - 10.1016/S0165-5728(97)00098-2
M3 - Article
C2 - 9307242
AN - SCOPUS:0342618656
SN - 0165-5728
VL - 78
SP - 172
EP - 179
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
IS - 1-2
ER -