Increased frequency of CD8 positive gamma/delta T-lymphocytes (CD8+γ/δ+) in unmedicated schizophrenic patients: relation to impairment of the blood–brain barrier and HLA-DPA*02011

Technische Universität München, München, Bavaria, Germany
Schizophrenia Research (Impact Factor: 3.92). 07/1998; 32(1):69-71. DOI: 10.1016/S0920-9964(98)00036-X
Source: PubMed
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    • "Vit D is also known to have regulatory effects on the activity and levels of gamma–delta (γδ) T cells (Chen et al., 2005). There is one study on γδ T cells in schizophrenia, showing an increase in γδ T cells in an unmedicated sample (Muller et al., 1998). Recent data suggests that γδ T cells develop as particular subsets, which predominantly produce IFNγ or IL‐17 (Shibata, 2012). "
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    ABSTRACT: In 1995, the macrophage-T lymphocyte theory of schizophrenia (Smith and Maes, 1995) considered that activated immuno-inflammatory pathways may account for the higher neurodevelopmental pathology linked with gestational infections through the detrimental effects of activated microglia, oxidative and nitrosative stress (O&NS), cytokine-induced activation of the tryptophan catabolite (TRYCAT) pathway and consequent modulation of the N-methyl d-aspartate receptor (NMDAr) and glutamate production. The aim of the present paper is to review the current state-of-the art regarding the role of the above pathways in schizophrenia. Accumulating data suggest a powerful role for prenatal infection, both viral and microbial, in driving an early developmental etiology to schizophrenia. Models of prenatal rodent infection show maintained activation of immuno-inflammatory pathways coupled to increased microglia activation. The ensuing activation of immuno-inflammatory pathways in schizophrenia may activate the TRYCAT pathway, including increased kynurenic acid (KA) and neurotoxic TRYCATs. Increased KA, via the inhibition of the α7 nicotinic acetylcholine receptor, lowers gamma-amino-butyric-acid (GABA)ergic post-synaptic current, contributing to dysregulated glutamatergic activity. Hypofunctioning of the NMDAr on GABAergic interneurons will contribute to glutamatergic dysregulation. Many susceptibility genes for schizophrenia are predominantly expressed in early development and will interact with these early developmental driven changes in the immuno-inflammatory and TRYCAT pathways. Maternal infection and subsequent immuno-inflammatory responses are additionally associated with O&NS, including lowered antioxidants such as glutathione. This will contribute to alterations in neurogenesis and myelination. In such a scenario a) a genetic or epigenetic potentiation of immuno-inflammatory pathways may constitute a double hit on their own, stimulating wider immuno-inflammatory responses and thus potentiating the TRYCAT pathway and subsequent NMDAr dysfunction and neuroprogression; and b) antipsychotic-induced changes in immuno-inflammatory, TRYCAT and O&NS pathways would modulate the CNS glia-neuronal interactions that determine synaptic plasticity as well as myelin generation and maintenance.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2012; 42. DOI:10.1016/j.pnpbp.2012.06.014 · 3.69 Impact Factor
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    ABSTRACT: Schizophrenia has often been observed to be associated with alterations of the cellular immune system. In this study we monitored numerous immune parameters in the course of antipsychotic treatment. 40 patients diagnosed with an acute exacerbation of schizophrenia were tested before and during treatment with antipsychotics. The percentual distribution of lymphocyte subgroups (CD3, CD4, CD8, CD19, CD5, CD16/56, CD25, HLA-DR, gd, CD11a, CD11b and CD49d) was measured by FACS analysis. 20 healthy volunteers served as controls. In the acute state of psychosis a significant elevation of the B-lymphocyte fraction was observed, while the percentage of T-lymphocytes was decreased. These values levelled to those of the control group in the course of treatment. Natural killer cells, integrine expressing cells and CD5+ B-cells showed alterations in numbers after several months of treatment. The latter may be a side effect of antipsychotic treatment. The findings in the acute state of schizophrenia could be seen as a nonspecific stress reaction or an effect of the altered metabolism of neurotransmitters. On the other hand the observed changes in the immune system could be due to infectious diseases or autoimmune processes provoking the symptoms of schizophrenia. Es wurde vielfach beobachtet, dass Schizophrenie mit Veränderungen der zellulären Immunität assoziiert ist. Im Rahmen dieser Arbeit sollte der zeitliche Verlauf mehrerer Immunparameter unter antipsychotischer Therapie näher betrachtet werden. Hierzu wurden 40 Patienten mit einer akuten schizophrenen Episode vor und während einer medikamentösen Therapie untersucht. Mittels Durchflußzytometrie wurden die Anteile verschiedener lymphozytärer Subgruppen (CD3, CD4, CD8, CD19, CD5, CD16/56, CD25, HLA-DR, gd, CD11a, CD11b und CD49d) bestimmt. Als Vergleichskollektiv dienten 20 gesunde Probanden. In der akuten Phase der Psychose zeigte sich ein erhöhter prozentualer Anteil an B-Lymphozyten sowie ein erniedrigter T-Zell Anteil. Im Laufe der Behandlung gleichen sich diese Werte an die der Kontrollgruppe an. Bezüglich NK-Zellen, Integrin-exprimierender Zellen und CD5+ B-Zellen ließen sich Veränderungen nach mehrmonatiger Untersuchungsdauer feststellen. Letzteres könnte Effekt der medikamentösen Therapie sein. Ob die Veränderungen im Akutstadium der Psychose als Reaktion auf die Erkrankung, sei es im Sinne einer unspezifischen Streßantwort oder als Auswirkung des veränderten Neurotransmitterstoffwechsel oder aber als Zeichen eines autoimmunen oder infektiösen Geschehens und damit als ursächlich für die Erkrankung gewertet werden sollen, bleibt zu diskutieren.
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    ABSTRACT: Immune alterations in schizophrenia have been described for decades. Modern immunological methods and new insights into the highly developed and functionally differentiated immune system allow an integrative view of both the older and the recent findings of immunological abnormalities in schizophrenia. Both the unspecific and the specific arms of the immune system seem to be involved in the dysfunction of the immune system in schizophrenia. The unspecific, “innate” immune system shows signs of over-activation in unmedicated schizophrenic patients, as indicated by increased monocytes and δ-cells. Increased levels of interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of monocytes/macrophages, too. On the other hand, several parameters of the specific cellular immune system are blunted, such as, for example, the decreased T helper-1 (TH-1)-related immune parameters in schizophrenic patients both in vitro and in vivo. It seems that a TH-1-TH-2 imbalance with a shift to the TH-2 system is associated with schizophrenia. During antipsychotic therapy with neuroleptics, the specific TH-1-related immune answer becomes activated, but in addition the B cell system and antibody production increase.
    Annals of the New York Academy of Sciences 12/1999; 917(1):456 - 467. DOI:10.1111/j.1749-6632.2000.tb05410.x · 4.38 Impact Factor
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