OLIGOCLONAL
EXPANSION OF T CELLS IN THE BRAIN OF CHILDREN WITH AIDS
J.E. Fincke1, W.L. Lin1, C.A. Slachta1,
L. Sharer2, C.D. Platsoucas1,
and E.L. Oleszak3*. Dept Microbiol &
Immunol1, Fels Institute Cancer Research
and Molecular Biology and Depts Anatomy & Cell Biol, &
Neurology3, Temple Univ Sch Med,
Philadelphia , PA; Div Neuropathol, Dept Pathol Lab Med, UMDNJ,
Newark, NJ2
To determine whether T cells
infiltrating the brains of children with AIDS contain monoclonal
populations of T cells, we amplified, by the non-palindromic
adaptor-PCR method b -chain TCR transcripts from autopsy
brains of two pediatric patients with AIDS. We cloned and
sequenced the amplified transcripts. Sequence analysis of b
-chain TCR transcripts from one patient revealed multiple
identical copies of three TCR b -chain transcripts. The clonal expansions
were confirmed using an independent amplification method (Vb
-specific PCR). Those TCR transcripts that were found to be
clonally expanded by NPA-PCR were also clonally expanded after Vb
-specific PCR. Sequence analysis of b -chain
transcripts from brain tissue of a second pediatric patient with
AIDS after NPA-PCR amplification and cloning, also revealed
multiple identical copies of b -chain transcripts. These sequences are
novel. Normal peripheral blood mononuclear cells (PBMC) were used
as control, and all TCR transcripts amplified by either NPA-PCR,
or Vb 5- or Vb 21-specific PCR were unique when compared
to each other, as anticipated for polyclonal populations of T
cells. The presence of oligoclonal populations of T cells in the
brain of these two pediatric patients with AIDS suggests that
these T cells have undergone antigen-driven proliferation and
clonal expansion to as-yet-unknown antigens. Although the
specificity of the clonally expanded b -chain TCR
transcripts remains to be elucidated, none of them were identical
to those specific for HIV-1 antigens that are currently reported
in the GENBANK/EMBL databases. T cells using these transcripts
may play a role in the pathogenesis of the disease, and, in
particular, in endothelial cell injury and the opening of the
blood-brain-barrier of HIV-1 infected children.