Presence of oligoclonal T cells in cerebrospinal fluid of a child with multiphasic disseminated encephalomyelitis following hepatitis A virus infection

We have investigated the clonality of beta -chain T-cell receptor (TCR) tra nscripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-y ear old child who developed a multiphasic disseminated encephalomyelitis fo llowing an infection with hepatitis A virus. We amplified beta -chain TCR t ranscripts by nonpalindromic adaptor (NPA)-PCR-V beta -specific PCR. TCR tr anscripts from only five V beta families (V beta 13, V beta3, V beta 17, V beta8, and V beta 20) were detected in CSF. The amplified products were com bined, cloned, and sequenced. Sequence analysis revealed in the CSF substan tial proportions of identical beta -chain of TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of 35 (48%) transcripts were 100% identical, demonstrating a major V beta 13.3 D beta2.1 J beta1.3 clon al expansion. Six of 35 (17%) transcripts were also 100% identical, reveali ng a second V beta 13 clonal expansion (V beta 13.1 D beta2.1 J beta1.2). C lonal expansions were also found within the V beta3 family (transcript V be ta3.1 D beta2.1 J beta1.5 accounted for 5 of 35 transcripts [14%]) and with in the V beta 20 family (transcript V beta 20.1 D beta1.1 J beta2.4 account ed for 3 of 35 transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal expansions in the CSF of this patient following infecti on with hepatitis A virus. Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell clones exhibited substantial homology to myel in basic protein-reactive T-cell clones. In contrast, all V beta TCR famili es were expressed in peripheral blood lymphocytes. Oligoclonal expansions o f T cells were not detected in the peripheral blood of this patient. It rem ains to be determined whether these clonally expanded T cells are specific for hepatitis A viral antigen(s) or host central nervous system antigen(s) and whether molecular mimicry between hepatitis A viral protein and a host protein is responsible for demyelinating disease in this patient.