Gt. Seah et Gaw. Rook, IL-4 influences apoptosis of mycobacterium-reactive lymphocytes in the presence of TNF-alpha, J IMMUNOL, 167(3), 2001, pp. 1230-1237
T cell apoptosis is associated with defective cell-mediated effector functi
ons in several infectious diseases. In tuberculosis, there is evidence that
T cell apoptosis may be cytokine mediated, but the mechanisms are not clea
rly understood. Type 2 cytokines have recently been associated with disease
extent in human tuberculosis, but they have not previously been linked to
apoptosis in mycobacterium-reactive T cells. This study presents evidence t
hat PBLs from healthy donors respond to sonicated Mycobacterium tuberculosi
s Ags with increased IL-4 gene activation, CD30 expression, and apoptosis.
The changes were significantly greater than those observed when cells were
stimulated with Ags from nonpathogenic Mycobacterium vaccae. A hypothesis l
inking these observations was tested. CD30 expression and TNF-alpha -mediat
ed lymphocyte apoptosis were both down-regulated by inhibiting IL-4 in this
model. TNFR-associated factor 2 (TRAF2) expression was down-regulated in C
D30(+) cells, and addition of anti-TNF-alpha Ab significantly reduced apopt
osis in the CD30(+) but not the CD30(-) population. These observations supp
ort the hypothesis that increased IL-4 expression in M. tuberculosis-activa
ted lymphocytes promotes CD30 expression, which sensitizes the lymphocytes
to TNF-alpha -mediated apoptosis via TRAF2 depletion. This may be one mecha
nism by which IIA is associated with immunopathological consequences in hum
an tuberculosis.