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Departments of Internal Medicine, Microbiology, and Immunology, Division of Infectious Diseases, University of Kentucky and Veterans Administration Medical Center, Lexington, KY 40506
Initiation of the pulmonary inflammatory response to
Pneumocystis carinii is delayed by 3 wk in mice infected
as neonates compared with adults. There was no difference in the
proliferative response of draining lymph node T cells from mice
infected as neonates compared with adults when stimulated in vitro with
either Con A or anti-CD3 mAb. However, TNF-
and IFN-
mRNA
expression in the lungs of P. carinii-infected neonates
was significantly lower than in adults indicating a lack of appropriate
activation signaling in the local environment. This may have been due
to active suppression because TGF-
mRNA expression was significantly
elevated in neonatal lungs compared with adults. To determine whether T
cells from 10-day-old mice would effect resolution of P.
carinii if harbored in an adult lung environment, cells were
adoptively transferred to SCID mice with established P.
carinii infections. There was no difference in the kinetics of
T cell migration into the lungs or of clearance of P.
carinii organisms when SCID mice were reconstituted with
splenocytes from young mice as compared with adult mice. Furthermore,
splenocytes from young mice stimulated both TNF-
and IFN-
mRNA
expression to levels that were similar to that in the lungs of SCID
mice reconstituted with adult cells. These data indicate that neonatal
lymphocytes are competent to resolve P. carinii
infection when harbored in an adult lung environment, suggesting that
the neonatal lung environment, and not the T cells, is ineffective at
responding to P. carinii
infection.
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