Impaired measles virus-specific cytotoxic T cell responses in multiple sclerosis.

Abstract

Multiple sclerosis (MS) l is a chronic demyelinating disease of the central nervous system (CNS) which can have a highly variable clinical course. While the etiology of this disorder is unknown, the majority of current research in this field is focussed on the elucidation of an infectious agent, an autoimmune process, or a combination of the two (1, 2). Numerous studies (1-4) have demonstrated immune abnormalities in MS. However, the majority of these reports have employed assays that either measured an aspect of cellular recognition without consideration of function (eg. lympboproliferative assays), or assessed the function of antigen-nonspecific cell activity, such as natural killer (NK) cell activity. Little is known of those populations of cells that are antigen-specific and have a demonstrable function, such as cytotoxic T cells (CTL) or T helper cells, which regulate T or B cell functions.Measles virus has been considered as a possible etiological factor in the pathogenesis of MS, based primarily on serological findings (5-8). For the most part, assays designed to demonstrate a functional cellular immune response to this agent (eg. CTL) have been unsuccessful, and consequently, the assessment of such antigen-specific immune responses in MS patients has not been possible. Using T cell clones (9, 10) and bulk culture populations (lacobson, S., M. L. Flerlage, and H. F. McFarland, manuscript in preparation) 2, we have shown that measles virus-specific CTL have a cell surface phenotype that was OKT4 +, and that they lysed infected cells by recognition of measles virus antigen in association with HLA class II molecules. To determine whether a measles virus-specific cellular immune abnormality is associated with MS, we analyzed the capacity of lymphocytes from MS patients to generate measles virus-specific CTL. In comparison, we have studied normal individuals and other disease controls (ODC). The vast majority of MS patients either failed to generate measles virus-specific CTL, or had significantly lower CTL responses than either normal individuals or ODC. Moreover, this decreased CTL response in MS patients was specific for This work was supported by postdoctoral fellowship grant FG 573 A-1 awarded to S. Jacobson from the National Multiple Sclerosis Society.a Abbreviations used in this paper: CNS, central nervous system; CTL, cytotoxic T ]ympbocytes; DSS, Kurtzke Disability Scale; EBV, Epstein-Barr virus; MS, multiple sclerosis; NK, natural killer; ODC, other disease controls; PBL, peripheral blood lymphocytes.~ Jacobson, S., and H. F. . Studies of measles virus specific, HLA class II restricted cytotoxic T lymphocytes generated in bulk culture. Abstract, Symposium on the Pathobiology and Immunopathology of Virus Infection Sendai, Japan.

HLA-DR specific monoclonal antibodies block lymphoproliferative response to measles vaccine in vitro: A pilot study

“…In late convalescence, the predominant population of cells is measles virus (MV)-specific CD4 + HLA class II-restricted cytotoxic T-lymphocytes (CTLs) [11]. This supports the observations found in this pilot study that HLA class II-restricted responses after immunization with measles appear to play a significant role in the development of CMI responses.…”

Mechanism of Neuroinflammation: Enhanced Cytotoxicity and IL-17 Production via CD46 Binding

“…Concurrently, aberrant T cell immunities against viral antigens of these two infectious agents have also been demonstrated in MS patients. Exposure of MS patient T cells to antigens of the Edmonston strain of the measles virus resulted in functional suppression of cyto-toxic CD4+ lymphocytes (Jacobson et al 1985). In contrast, infected HHV-6 strain U1102 cell lysate preparation induced proliferation and IFN-γ production in T cells of a subset of the MS patients (Soldan et al 2000).…”

Human T‐cell response to myelin basic protein in multiple sclerosis patients and healthy subjects

“…In MS, the pathogenetic role of T-cells is strongly suggested by the analysis of the mononuclear cell infiltrates, which comprised mostly T-cells and macrophages [Traugott , 19851. On the other hand, the antigens responsible for autoimmunization are so far unknown. The causative role of a putative viral agent remains a likely possibility, in view of epidemiological studies [Cook and Dowling , 19801 and of several reports demonstrating abnormal immune responses to some viral antigens in MS patients [Utermohlen and Zabrislue, 1973;Jacobson et al, 1985;Koprowski et al, 19851.…”