T cell response in malaria pathogenesis: selective increase in T cells carrying the TCR Vβ8 during experimental cerebral malaria

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Abstract
To characterize the T cells involved in the pathogenesis of cerebral malaria (CM) induced by infection with Plasmodium berghei ANKA clone 1.49L (PbA 1.49L), the occurrence of the disease was assessed in mice lacking T cells of either the αβ or γδ lineage (TCRαβ–/– or TCRγδ–/–). TCRγδ–/– mice were susceptible to CM, whereas all TCRαβ–/– mice were resistant, suggesting that T cells of the αβ lineage are important in the genesis of CM. The repertoire of TCR Vβ segment gene expression was examined by flow cytometry in B10.D2 mice, a strain highly susceptible to CM induced by infection with PbA 1.49L. In these mice, CM was associated with an increase of T cells bearing the Vβ8.1, 2 segments in the peripheral blood lymphocytes. Most Vβ8.1, 2+ T cells from peripheral blood lymphocytes of the mice that developed CM belonged to the CD8 subset, and exhibited the CD69+, CD44high and CD62Llow phenotype surface markers. The link between the increase in Vβ8.1, 2+ T cells and the neuropathological consequences of PbA infection was strengthened by the observation that the occurrence of CM was significantly reduced in mice treated with KJ16 antibodies against the Vβ8.1 and Vβ8.2 chains, and in mice rendered deficient in Vβ8.1+ T cells by a mouse mammary tumor virus superantigen.