Lymphocyte populations in Parkinson’s disease and in rat models of parkinsonism
Introduction
Idiopathic Parkinson’s disease (PD) is a degenerative neurological disorder of unknown etiology. Several pathogenic mechanisms have been proposed to cause neuronal death such as oxidative stress, mitochondrial dysfunction or metabolic impairment. The major neurochemical feature is the loss of dopamine in nigrostriatal pathway but perturbations in other neurotransmitter systems also occur, including noradrenergic and cholinergic, which are related with the regulation of the immune system. Actually, it is not known whether immune mechanisms have a role in neurodegenerative diseases. However, in the last years the implication of the immune system and chronic inflammation in the neuronal death has been suggested (McGeer and McGeer, 1995). In PD, some indications of a certain degree of intracerebral immune activation have been described. These include activated microglia in the substantia nigra (McGeer et al., 1988; McGeer and McGeer, 1997a), proinflammatory cytokines (Mogi et al., 1994; McGeer and McGeer, 1997b), and enhanced expression of HLA-DR antigens on CSF monocytes (Fiszer et al., 1994). In addition, several authors have described immunological alterations such as the presence of antibodies against dopaminergic neurons in serum (Defazio et al., 1994) and CSF (Carvey et al., 1991) of PD patients, and higher ADCC activity (Bokor et al., 1993). Less data are available on phenotypic alterations of circulating lymphocytes, but changes in the percentage of CD8+ cells and CD4+ subsets (Fiszer, 1989; Fiszer et al., 1994) have been reported. All these findings are suggestive of an ongoing immune response that could play a role in the pathogenesis of the disease; however, the existence of immune activation in peripheral blood remains controversial. Indirect signs of lymphocyte activation, such as increased adenosine deaminase activity, have been observed by some authors (Chiba et al., 1995), but defective production of interleukin-2 by peripheral blood lymphocytes has also been demonstrated (Kluter et al., 1995).
In this context, the present study was aimed to assess the composition of peripheral blood lymphocyte subsets and the presence of activated T cells in peripheral blood of PD patients. Furthermore, since the neuroendocrine regulation of the immune system could be impaired, we also assessed the role of dopamine in the described alterations of lymphocyte subsets. This was accomplished by comparing treated with untreated patients and by testing the effect of experimentally induced dopamine depletion in rats on the ‘in vivo’ activation of lymphocytes.
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Patients
Sixty-four patients controlled in the Movement Disorders Unit of the Neurology Department of our Center and meeting strict inclusion criteria were selected for the study. These criteria included to fulfill diagnostic criteria of idiopathic Parkinson’s disease (Calne et al., 1992) and the absence of central nervous system lesions by a CT scan. The exclusion criteria were the presence of diseases that could affect significantly the immunological parameters assessed, such as inflammatory
Peripheral blood T cell subsets in Parkinson’s disease
The analysis of lymphocyte subsets including all 64 patients showed lower lymphocyte counts in Parkinson patients than in control subjects (1839±577 vs. 2227±541; P=0.001) due to the decrease in the number of both T (CD3+) and B (CD19+) cells. As is shown in Table 2, the changes in T cells were caused by a decrease in the number of helper T cells (CD4+ lymphocytes) while its counterpart, the cytotoxic/suppressor CD8+ lymphocytes remained unchanged. When the results were expressed as percentages
Discussion
In recent years, a number of studies have suggested the involvement of immunological mechanisms in some neurodegenerative diseases, and this represents a conceptual challenge. The alterations in lymphocyte subsets have been widely described in autoimmune diseases, but data in neurodegenerative diseases such as PD are scarce. Our results are very interesting because they showed the depletion of some lymphocyte subsets in peripheral blood of PD patients and a certain degree of immunological
Acknowledgements
The authors thank Mr. Jordi Bonete and Mrs. Carme Salarich for his skillful technical assistance. We also thank Dr. A. Rubió for providing blood donor samples. Financial support from the ‘Fondo de Investigaciones Sanitarias de la Seguridad Social’, grant 94/1100.
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