Gamma interferon, but notMycobacterium leprae, induces major histocompatibility class II antigens on cultured rat Schwann cells

Abstract

In order to investigate the possible role of Schwann cells in immune reactions, and in particular their involvement in the response to infection with Mycobacterium leprae, it was determined under what conditions Schwann cells express major histocompatibility complex class II (MHC class II) antigens, since these molecules are thought to have a key role in antigen presentation during cellular immune responses. In situ and in vitro preparations from newborn and adult rat sciatic nerves were used as a model system to examine this question. Schwann cells in dissociated cell cultures did not express immunohistochemically detectable amounts of MHC class II antigens. Teased nerve preparations from the sciatic nerves of healthy adult rats showed no detectable immunolabelling of either myelin-forming or non-myelin-forming Schwann cells. When dissociated Schwann cell cultures derived from the sciatic nerves of either neonatal or adult rats were treated with 10, 50 or 100 units of gamma interferon, MHC class II antigens were detectable on the surface of some Schwann cells 48 h after addition of the interferon. By 72 h, 32.29 +/- 3.9% of Schwann cells in the cultures from neonatal rats and 53.32 +/- 5.4% of Schwann cells in cultures from adult rats, identified by the presence of intracellular S-100, were clearly MHC class II-positive, especially at doses of 50 and 100 units per ml of gamma interferon. Some, but not all, of the fibroblastic cells were very weakly MHC class II-positive. Infection of the cultures with Mycobacterium leprae did not induce MHC class II antigen expression in either Schwann cells or fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in the Capacity of Gamma-Interferons from Different Species to Induce Class I and II Major Histocompatibility Complex Antigens on Neonatal Rat Schwann Cells in vitro

“…This confirms our earlier work on class II antigens in rats [25] as well as that of others in rats and mice [8][9][10], Samuel et al [9] did detect very low levels of MHC class I antigen on neonatal Schwann cells but no evidence for class II antigens. Scarpini et al [18] and Yonget al [27] have recently noted the presence of MHC I and II antigens on cultures of human fetal Schwann cells as well as on adult Schwann cells obtained from 2 patients without any clinical or histologic evidence of neuropathy and 2 patients with neuropathy secondary to vasculitis [ 18], Others have not found MHC class II antigens on cul tured human fetal Schwann cells [9,28].…”

“…Unfractionated cytokines have been reported to induce Schwann cell pro liferation [3], Induction of synthesis of nerve growth fac tor by Schwann cells in vitro and in vivo has been demon strated using interleukin-1 (IL-1) produced by recombi nant DNA technology [4][5][6], IL-I is a monokine, occur ring in two isoforms, secreted by activated cells of the monocyte/macrophage lineage [7], y-Interferon (y-IFN), a August 24. 1991 lymphokine secreted by certain subsets of activated T lymphocytes, has been reported to induce both class I and II major (MHC) antigens on Schwann cells in vitro [8][9][10][11][12], There has been some controversy as to the capacity of Schwann cells and different types of central nervous sys tem glia to become MHC class II positive in vitro [3,13], Several factors may be involved including the age of the glial cells (maturation) and the species from which they are obtained as well as the species serving as the source of the cytokines. Class I and II MHC antigens have been reported in nerves of patients with diseases of the periph eral nervous system [2,[14][15][16][17][18][19].…”

In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules.

“…This treatment did, however, induce MHC class II expression on astrocytes (data not shown) (7,11,12) and would also be expected to induce MHC class II expression on Schwann cells (14) and 0-2A progenitor cells (10 …”

“…These cells and perinatal 0-2A progenitor cells can also be induced to express MHC class II molecules in response to y interferon (IFN-y) in vitro (4,7,(10)(11)(12). In the peripheral nervous system, IFN-y also induces MHC class II expression on Schwann cells, the glial cells of peripheral nerves (13,14). This effect may be of particular relevance in immune-related diseases, such as leprosy (15) Recombinant rat IFN-y and mouse anti-rat IFN-'y antibody (DB1) were provided by P. Van der Meide (24)…”

Major histocompatibility complex class II expression and macrophage responses in genetically proven Charcot-Marie-Tooth type 1 and hereditary neuropathy with liability to pressure palsies

“…20,27 MHC class II molecules are critically involved in antigen recognition by T cells 37 and can be induced by the cytokine interferon-gamma on mac-rophages and Schwann cells in culture. 1,28,40 Based on the increased expression of MHC class II molecules in sural nerves, responses of some cases to steroid treatment, 8,22 and elevated numbers of activated T cells in peripheral blood of CMT patients, 32,39 a role of immune mechanisms in mediating nerve damage has been proposed. Due to the lack of a genetic marker, all these studies relied on clinical and electrophysiological findings in establishing the diagnosis of CMT1.…”