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.
POSTER