Heterogeneity of CD4(+) and CD8(+) memory T cells in localized and generalized Wegener's granulomatosis

Memory T cells display phenotypic heterogeneity. Surface antigens
previously regarded as exclusive markers of naive T cells, such as
L-selectin ( CD62L), can also be detected on some memory T cells.
Moreover, a fraction of CD45RO(+) ( positive for the short human
isoform of CD45) memory T cells reverts to the CD45RA(+) ( positive
for the long human isoform of CD45) phenotype. We analyzed patients
with biopsy-proven localized Wegener's granulomatosis (WG) (n = 5),
generalized WG (n = 16) and age- and sex-matched healthy controls (
n = 13) to further characterize memory T cells in WG. The
cell-surface expression of CD45RO, CD45RA, CD62L, CCR3, CCR5 and
CXCR3 was determined on blood-derived T cells by four-color flow
cytometric analysis. The fractions of CCR5(+) and CCR3(+) cells
within the CD4(+) CD45RO(+) and CD8(+) CD45RO(+) memory T cell
populations were significantly expanded in localized and
generalized WG. The mean percentage of Th1-type CCR5 expression was
higher in localized WG. Upregulated CCR5 and CCR3 expression could
also be detected on a fraction of CD45RA(+) T cells. CD62L
expression was seen on approximately half of the memory T cell
populations expressing chemokine receptors. This study demonstrates
for the first time that expression of the inducible inflammatory
chemokine receptors CCR5 and CCR3 on CD45RO(+) memory T cells, as
well as on CD45RA(+) T cells ('revertants'), contributes to
phenotypic heterogeneity in an autoimmune disease, namely WG.
Upregulated CCR5 and CCR3 expression suggests that the cells belong
to the effector memory T cell population. CCR5 and CCR3 expression
on CD4(+) and CD8(+) memory T cells indicates a potential to
respond to chemotactic gradients and might be important in T cell
migration contributing to granuloma formation and vasculitis in WG.