CLONALLY EXPANDED T CELLS ARE PRESENT IN THE CSF OF PATIENTS WITH MAJOR DEPRESSION

CLONALLY EXPANDED T CELLS ARE PRESENT

IN THE CSF OF PATIENTS WITH MAJOR DEPRESSION

EL Oleszak1, WL Lin1,

JR Chang1, X Zhang1, S Herzog2, M Bhattacharjee3,

G  Rudner4, CD Platsoucas1, K. Bechter5

1Temple University School

of Medicine, Philadelphia; 2Glessen University, Germany; 3Tulane

University School of Medicine, New Orleans; 4Jefferson Parish

Forensic Center, New Orleans; 5University of Ulm, Germany

Viruses have long been implicated in

the etiology of certain psychiatric diseases.  Several immunological

abnormalities have been detected in the CSF and sera of patients with

schizophrenia and affective psychoses, including the presence of antibodies to

Borna Disease Virus (BVD) and others.  The objective of our studies was to

determine whether T cells present in the CSF of patients with schizophrenia and

affective psychosis are clonally expanded.  Oligoclonality of T cells would

suggest specific antigen-driven response.  We have analyzed the T-cell

receptor (TCR) repertoire in the CSF of two patients with major depression and

one patient with schizophrenia.  All patients were seropositive for

BDV.  Using nonpalindromic (NPA)-PCR/Vb-specific PCR amplification (CDLI

5:984-92, 2001), we detected TCR transcripts from 6 out of 24 Vb families in the

CSF of one patient with major depression.  Sequence analysis revealed that

the TCR transcripts belonged to the Vb2, Vb4, Vb5, Vb8, Vb10 and Vb7

families.  In contrast, all TCR transcripts sequenced from the peripheral

blood of the same patient were unique when compared to each other, in a manner

typical of polyclonal populations of T cells.  Only Vb4 and Vb6 transcripts

were found in the CSF of the second patient with major depression. 

Furthermore, 83% of the Vb4 transcripts in this patient were identical,

demonstrating the presence of a strong clonal expression of T cells in the CSF

of this patient.  Lastly, TCR transcripts of the Vb2, Vb6 and Vb14 families

were clonally expanded in the CSF of the patients with schizophrenia while TCR

transcripts from the remaining 21 Vb families were not detected.  In

contrast to the CSF, all b-chain TCR transcripts from the peripheral blood of

this patient with schizophrenia were polyclonal.  We have also analyzed TCR

repertoire in the CSF of two “normal” individuals without any

psychiatric or neurological diseases.  We have detected 12 Vb families and

all TCR transcripts were polyclonal.  The presence of clonally expanded T

cells in the CSF of patients with major depression and schizophrenia suggests a

specific antigen-driven T-cell response.  These T cells may recognize

either viral or host epitopes, possibly due to molecular mimicry.  These

clonally expanded TCR transcripts in the CSF of patients with major depression

and schizophrenia may permit the identification of the virus(es) potentially

involved in the pathogenesis of these diseases.

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