Journal of Neurological Sciences 149 (1997) 41–45 T-lymphocyte tumor necrosis factor-a receptor binding in patients with Parkinson’s disease a, a a a b * P. Bongioanni , M. Castagna , S. Maltinti , B. Boccardi , F. Dadone a Scuola Superiore di Studi Universitari e di Perfezionamento, Sant’ Anna, Via Carducci 40, 56123, Pisa, Italy b Neuropsychiatry Service, Ceva Hospital, Ceva ( CN), Italy Received 13 August 1996; revised 12 December 1996; accepted 30 December 1996 Abstract Parkinson’s disease (PD) is a neurodegenerative disease of the central nervous system (CNS), in which the cytokine network may be deranged, leading to an altered immunoregulation. Tumor necrosis factor(TNF)-a, a cytokine with pleiotropic neuroimmune effects, has specific receptors on human lymphocytes, as well as on other cell types, even in the CNS. The aim of the present study was to assay TNF-a binding on peripheral blood T cells from PD patients, as compared with healthy subjects. We found on T lymphocytes from parkinsonian patients significantly more TNF-a receptors than on those from controls ( B : 637623 vs. 13166 (mean6S.E.M.) max receptors / cell). Such TNF-a binding sites are of the same type in patients and healthy subjects ( K : 66.865.1 vs. 70.765.6 d (mean6S.E.M.) pM). These results are discussed in terms of PD immunopathogenesis, since it has been reported that activated T lymphocytes have increased amounts of TNF-a receptors.  1997 Elsevier Science B.V. Keywords: Cytokines; Immune response; Lymphocytes; Neurodegenerative diseases; Parkinson’s disease; T cells; Tumor necrosis factor 1. Introduction amino-acid long 17 kDa protein, plays an important neuroimmunological role (Aggarwal, 1992; Nicola, 1994). Parkinson’s disease (PD) is a neurodegenerative disease It has been reported that TNF-a induces the differentiation characterized clinically by muscle rigidity, akinesia / and growth arrest of neuroblastoma cells, but enhances the bradykinesia, tremor and postural instability. The typical growth of glioma cells (Munoz-Fernandez et al., 1991) and pathological picture includes depigmentation, loss of neu- the astrocyte proliferation (Selmaj et al., 1990), stimulates rons and neuronal cytoplasmic inclusions (Lewy bodies) in interleukin(IL)-6 production within the CNS (Frei et al., the substantia nigra (Jellinger, 1987). Neurochemically, 1989) and damages oligodendrocytes (Selmaj and Raine, there is a central dopamine deficiency. 1988). TNF-a also modulates the expression of major The pathogenesis of PD is still unclear, but immune histocompatibility complex (MHC)-class I and II mole- mediated events might be involved (Jankovic and Kusic, cules on gliocytes (Mauerhoff et al., 1988; Bongioanni, 1 1989). Cytokines represent important modulators of cell- 1991): antigen presentation by MHC astrocytes could to-cell interactions, even in the central nervous system enhance the local immune response. (CNS) (Ransohoff and Benveniste, 1996). The abnormali- Mogi et al. (1994) reported that TNF-a is increased ty in the immune response found in PD patients may both in the striatum and in the cerebrospinal fluid from PD depend, indeed, on a derangement in the cytokine network. patients. Boka et al. (1994) detected TNF-immunoreactive Among cytokines, tumor necrosis factor(TNF)-a, a 157 glial cells in the substantia nigra of parkinsonian patients but not in that of control subjects. Such data suggest that in PD an immune response may occur in the nigrostriatal * Corresponding author. Tel.: 139 (50) 883247; fax: 139 (50) 883215. dopaminergic regions, and that TNF-a may be involved, at 0022-510X / 97 / $17.00  1997 Elsevier Science B.V. All rights reserved PII S0022-510X(97)05382-3