T-cell receptor identification of an oligodendrocyte-specific autoreactive cytotoxic T-cell clone without self restriction.

In addition to myelin basic protein (MBP) and proteolipid protein (PLP), oligodendrocyte (Od) membrane autoantigens, such as the glycoprotein M2/MOG, could participate in the pathogenesis of autoimmune demyelinating diseases of the central nervous system (CNS), such as experimental allergic encephalomyelitis (EAE) or multiple sclerosis (MS). We have described an Od-specific autoreactive and cytotoxic T-cell clone, named C2, which recognized M2/MOG without conventional MHC restriction. In order to analyse the Od/C2 interaction, we determined the alpha/beta T-cell receptor (TCR) variable region usages and structures of C2.

Oligodendrocyte-specific autoreactive T cells using an alpha/beta T-cell receptor kill their target without self restriction.

The oligodendrocyte (Od), a glial cell that produces myelin in the central nervous system, may be a target for autoreactive T cells in autoimmune demyelinating processes, although not expressing major histocompatibility complex (MHC) products. To analyze Od-T-cell interactions, we selected from normal SJL/J mouse splenocytes sensitized in vitro by Lewis rat Od a T-cell clone, named C2, exhibiting a surface phenotype of mature T cell (Thy 1+, CD3+, CD8+, CD4-, asialo-GM1-). C2 T cells displayed a specific cytotoxicity to syngeneic Od as well as to rat Od, but not to astrocytes or lymphoblasts, or to YAC-1 cells, a target for natural killer and lymphokine-activated killer activity.

Lymphocyte proliferative response to glial cells in SJL/J mice immunized with rat whole spinal cord and rat myelin basic protein.

Lymph node cells (LNC) from SJL/J mice immunized with either rat whole spinal cord (WSC) homogenate or rat myelin basic protein (MBP) in the presence of complete Freund's adjuvant were assayed for their in vitro proliferative response to MBP and whole or sonicated purified oligodendrocytes (OD), and astrocytes. WSC-immunized mice displayed a strong and persistent response to both syngeneic and rat OD, that disappeared after sonication (suggesting a preferential recognition of surface OD antigen(s], and a much weaker response to rat MBP. LNC from MBP-immunized mice showed a small response to MBP, but no response to OD, indicating that OD are not able to present their endogenous MBP to lymphocytes.

Non-MHC-restricted, tissue-specific T cells recognizing autologous oligodendrocytes in the normal SJL/J mouse.

The oligodendrocyte (OD), a glial cell that produces myelin in the central nervous system (CNS), represents a possible target for autoreactive T cells in autoimmune demyelinating processes. To analyze OD/T lymphocyte interactions, we sensitized in vitro SJL/J mouse spleen cells (SC) over Lewis rat OD cultures and maintained them as long-term T-cell lines in interleukin-2 (IL-2)-containing medium. The proliferative response of these lines could be elicited by syngeneic OD as well as by Lewis rat OD, but appeared to be tissue-specific since SC failed to trigger their proliferation.