Recognition of major histocompatibility complexantigens on murine glial cells

Abstract

Recognition of autologous major histocompatibility complex (MHC) antigens by T cells is an essential step in the induction of an immunologic reaction to either endogenous or exogenous antigens. We investigated the ability of murine glial cells of different ages to stimulate clones of allospecific T lymphocytes. We also investigated the effects of supernatants from cultures of activated T cells on the immunologic recognition of MHC antigens on murine glial cells. Lymphocyte clones specific for Class I, Class II and non-MHC, background antigens were obtained from C57B1/6J-anti-DBA/2 mixed lymphocyte cultures. Glial cell cultures were prepared from newborn syngeneic (C57B1/6J) and allogeneic (DBA/2) mouse brains. Glial cultures 1-4 weeks of age were able to stimulate alpha-Class I-specific clones. No stimulation of alpha-Class II or alpha-background clones was noted. Incubation of glial cells with supernatants from cultures of alloantigen-activated spleen cells (C57B1/6J-anti-DBA/2) resulted in a decreased ability of glial cells to stimulate alpha-Class I responses. In contrast supernatant-treated cultures acquired the capacity to stimulate alpha-Class II-specific clones. No responses were noted in clones responsive to non-MHC antigens. The ability to stimulate alpha-Class II-specific clones was most prominent with one-week-old glial cultures and was lost by four weeks of culture. The increased susceptibility of younger glial cultures to the modulatory effects of lymphokines from activated T cells may be a factor in the increased susceptibility of the immature central nervous system to persistent viral infections and the development of autoimmune phenomena.

Transplantation of a temperature‐sensitive, nerve growth factor‐secreting, neuroblastoma cell line into adult rats with fimbria–fornix lesions rescues cholinergic septal neurons

“…A require-ment for immunological rejection is that the transplanted cell express appropriate foreign and MHC antigens (Streilein, 1988;Zinkernagel and Doherty, 1974). Astrocytes and microglial cells can express both class I and I1 MHC antigens (Akiyama et al, 1988;Birnbaum et al, 1986;Grenier et al, 1989;Tedeschi et al, 1986;Wong et al, 1984), and oligodendrocytes can express class I MHC antigens (Grenier et al, 1989;Kim et al, 1985) after treatment of these various CNS cell types with IFNy or other immune modulatory cytokines. In contrast, CNS neurons cannot be induced to express either class I or I1 MHC antigens Suzumura et al, 1986;Tedeschi et al, 1986), making them more suitable for CNS transplantation since they may not be recognized as immmunologically foreign and subsequently rejected by CTLs.…”

Analysis of Major Histocompatibility Complex Gene Products in Tissues Isolated from the Developing Human Nervous System

“…The cellular expression of gene products of the MHC locus is re quired for T cell-mediated immune reac tions in that the level of this expression affects the sensitivity of T lymphocytes to function in the cell-mediated immune re sponse [32], Whether cells outside the im mune system, in particular those of the ner vous system (glial and endothelial cells), function in the processing or presentation of antigen is still under investigation [33], Nixon et al [15] demonstrate antigen pre sentation by nonimmune cells other than cells of nervous system tissues, suggesting that presentation of self or novel antigens by nonimmune cells may result in an autoim mune response. The basis for this postula tion is the induction of MHC class I and II antigen expression in nonimmue cells [34] and the proliferation of T cell lines that rec ognize these MHC antigens [35,36]. Recent studies have begun to focus on the ability of neural cells to express MHC and subse quently to function as immunocompetent cells.…”

Immune actions in the nervous system: A brief review with special emphasis on Aalzheimer's disease

“…The major contenders are astrocytes and microglia, with only two groups suggesting involvement of oligodendrocytes [Kim et al, 1985;Ting et al, 19811. Most groups who have identified Ia-positive cells as astrocytes have done so on morphologic grounds [Birnbaum et al, 1986;de Tribolet et al, 1984;Lampson and Hickey, 1986;Traugott et al, 1984, 19861 or have identified the antigens immunocytochemically on dissociated, cultured central nervous system cells that may or may not be typical of glial cells in vivo [Birnbaum, et al, 1986;de Tribolet et al, 1984;DuBois et al, 1985;Frank et al, 1986;Hirsch et al, 1983;Kim et al, 1985;Wong et al, 19851. de Tribolet and colleagues [de Tribolet et al, 1984;Frank et al, 1986) have used double staining with Ia antibody and glial fibrillary acidic protein (GFAP) (a marker for astrocytes) on central nervous system metastatic tissue to show conclusively that astrocytes (GFAP-positive cells) can express Ia. The authors do not, however, rule out expression of Ia by some niicroglial cells.…”