T cell response in malaria pathogenesis: selective increase in T cells carrying the TCR V(beta)8 during experimental cerebral malaria

To characterize the T cells involved in the pathogenesis of cerebral malari a (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 o f either the alpha beta or gamma delta lineage (TCR alpha beta(-/-) or TCR gamma delta(-/-)). TCR gamma delta(-/-) mice were susceptible to CM, wherea s all TCR alpha beta(-/-) mice were resistant, suggesting that T cells of t he ap lineage are important in the genesis of CM, The repertoire of TCR Vp segment gene expression was examined by flow cytometry in B10.D2 mice, a st rain 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 V(beta)8.1 , 2 segments in the peripheral blood lymphocytes, Most V(beta)8.1, 2(+) T c ells from peripheral blood lymphocytes of the mice that developed CM belong ed to the CD8 subset, and exhibited the CD69(+), CD44(high) and CD62L(low) phenotype surface markers, The link between the increase in V(beta)8.1, 2() T cells and the neuropathological consequences of PbA infection was stren gthened by the observation that the occurrence of CM was significantly redu ced in mice treated with KJ16 antibodies against the V(beta)8.1 and V(beta) 8.2 chains, and in mice rendered deficient in V(beta)8.1(+) T cells by a mo use mammary tumor virus superantigen.