The anaphylatoxin C5a is a potent mediator of inflammation that exerts a br
oad range of activity on cells of the myeloid lineage, In this study, we pr
esent the first evidence that human T cells express the C5a receptor (C5aR)
and are chemotactic to C5a, Using FAGS analysis, we found that the C5aR wa
s expressed at a low basal level on unstimulated T cells and was strikingly
up-regulated upon PHA stimulation in a time- and dose-dependent manner. CD
3(+) sorted T cells as well as Jurkat T cells were shown to express C5aR mR
NA as assessed by RT-PCR, Moreover, semiquantitative RT-PCR analysis demons
trated that C5aR mRNA was do downregulated in purified T cells upon long-te
rm PHA stimulation. To demonstrate that C5a was biologically active on T ce
lls, we investigated the chemotactic activity of C5a and observed that puri
fied CD3+ T cells are chemotactic to C5a at nanomolar concentrations. Final
ly, using a combination of in situ hybridization and immunohistochemistry,
we showed that the T cells infiltrating the central nervous system during e
xperimental allergic encephalomyelitis express the C5aR mRNA, In summary, t
hese results suggest that C5a exerts direct effects on T cells and could be
involved in the trafficking of T cells under physiological and pathologica
l conditions, including inflammatory diseases of the central nervous system
.