Oligoclonal T cells are infiltrating the brains of children with AIDS: sequence analysis reveals high proportions of identical beta-chain T-cell receptor transcripts

Abstract

We have recently described the presence of perivascular CD3+ CD45RO+ T cells infiltrating the brains of children with AIDS. To determine whether these infiltrates contain oligoclonal populations of T cells, we amplified by PCR beta-chain T-cell receptor (TCR) transcripts from autopsy brains of four paediatric patients with AIDS. The amplified transcripts were cloned and sequenced. Sequence analysis of the beta-chain TCR transcripts from all four patients revealed multiple identical copies of TCR beta-chain transcripts, suggesting the presence of oligoclonal populations of T-cells. These TCR transcripts were novel. The presence of oligoclonal populations of T cells in the brains of these four paediatric patients with AIDS suggests that these T cells have undergone antigen-driven proliferation and clonal expansion very likely in situ, in the brains of these AIDS patients, in response to viral or self-antigens. Although the specificity of the clonally expanded beta-chain TCR transcripts remains to be elucidated, none of the beta-chain TCR transcripts identified in this study were identical to those specific for HIV-1 antigens that are currently reported in the GENBANK/EMBL databases. Certain common CDR3 motifs were observed in brain-infiltrating T cells within and between certain patients. Large proportions (24 of 61; 39%) of beta-chain TCR clones from one patient (NP95-73) and 2 of 27 (7%) of another patient (NP95-184-O) exhibited substantial CDR3 homology to myelin basic protein (MBP)-specific TCR derived from normal donors or TCR expressed in the brain of patients with multiple sclerosis (MS) or with viral encephalitis. These two patients (NP95-73 and NP95-184-O) also shared HLA class II with the normal donors and the MS patients who expressed these homologous TCR. Pathologic examination at autopsy of the brains revealed the presence of myelin pallor only in patient NP95-73. T-cell clones identified in the brain of patients NP95-73 and NP95-184-O may recognize MBP or another CNS self antigen and this recognition may be restricted by either DRB1*15 or DQB1*0602 specificities.