EFFECT OF HUMAN LUNG ALLOGRAFT ALVEOLAR MACROPHAGES ON IGG PRODUCTION- IMMUNOREGULATORY ROLE OF INTERLEUKIN-10, TRANSFORMING GROWTH-FACTOR-BETA, AND INTERLEUKIN-6
Ds. Wilkes et al., EFFECT OF HUMAN LUNG ALLOGRAFT ALVEOLAR MACROPHAGES ON IGG PRODUCTION- IMMUNOREGULATORY ROLE OF INTERLEUKIN-10, TRANSFORMING GROWTH-FACTOR-BETA, AND INTERLEUKIN-6, American journal of respiratory cell and molecular biology, 13(5), 1995, pp. 621-628
Alveolar macrophages (AM) are crucial to initiating and maintaining lo
cal immune responses. The increased susceptibility to pulmonary infect
ions in lung allograft recipients may be due to impaired AM function r
esulting in diminished cellular and humoral immunity, We have previous
ly reported that control AM were potent stimulators of IgG production
from allogeneic peripheral blood mononuclear cells (PBM) in a manner t
hat was dependent on gamma-interferon (gamma IFN), The ability of allo
graft AM to induce IgG production is unknown, The purpose of the curre
nt study was to compare the ability of allograft and control AM to ind
uce IgG production from allogeneic PBM. In contrast to control AM whic
h induced a dose-dependent stimulation of IgG production from allogene
ic PBM, allograft AM were highly suppressive of IgG production. The in
hibition was not due to a lack of allograft AM stimulation of gamma IF
N production from responding lymphocytes. Supernatants from allograft
AM were highly suppressive of control AM-induced IgG production. Allog
raft AM produced greater quantities of interleukin (IL-10) than contro
l AM while transforming growth factor-beta (TGF-beta) production from
these cells was comparable. Blocking antibodies to IL-10 and TGF-beta
reversed the inhibition of IgG production to 63% and 60% of control, r
espectively. In addition, the production of interleukin 6 (IL-6), a ma
crophage-derived cytokine crucial to the stimulation of IgG synthesis,
was deficient in the allograft AM. Addition of IL-6 to allograft AM a
nd allogeneic PBM co-cultures restored IgG synthesis. These data sugge
st that impaired IL-6 production in combination with IL-10 and TGF-bet
a synthesis by allograft AM may prevent adequate IgG responses to path
ogens in vivo.