Abstracts (complete list) - Wissenschaft Online

Christof Iking-Konert, Tim Vogl, Matthias Schneider, Konrad Andrassy, Gertrud Maria
Hansch
T-lymphocytes in patients with primary vasculitides:
Expression of CD11b identifies activated T cells with the
propensity to stimulate polymorphonuclear neutrophils
Objetive
To gain insight into the immune pathogenesis of primary, ANCA-associated vasculitides
(AAV) T-lymphocytes of patients were analysed with regard to the expression of
molecules indicative for current or previous activation. T-lymphocytes of patients with
Wegener's granulomatosis (WG; n= 47), or microscopic polyangiitis (MPA; n=33) in
remission were phenotypically and functionally analysed, and compared to Tlymphocytes
of patients with active disease (n=10), and to cells of healthy donors. In
vitro, T-cells of a similar phenotype were generated, and their interaction with
polymorphonuclear neutrophils (PMN) was assessed.
Results
During active disease, a small, but conspicuous population of CD8+CD28+CD11b+ was
found, which produced gamma interferon.Under immunosuppressive therapy, CD11b
was exclusively seen on CD8+CD28- cells, the latter being more frequent in patients
with long-lasting or severe disease. In vitro experiments confirmed that CD11b is upregulated
by activated T-cells, concomitantly with synthesis of gamma interferon.
During prolonged culture, CD11b remains on the surface, even when CD28 is lost,
compatible with the notion that CD8+CD28+CD11b+ represent a transient phenotype in
the course of T-cell activation. In vitro, the gamma interferon-producing T cells
activated PMN to express CD64 and MHC class II molecules, thus generating the same
PMN-phenotype as it is seen in patients with active ANCA-associated vasculitis. Of note
is that a similar phenotype could be generated by supernatants of activated T-cells, or
by gamma interferon alone, but not by antibodies to proteinase 3.
In conclusion, CD11b expression identifies activation of a small population of CD8+Tcells
during active primary vasculitis. By producing gamma interferon, these T-cells
could activate PMN by a “cross talk” between PMN and T-cells, thus generating a longliving
and potentially destructive PMN phenotpye.