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.