Interleukin-12 neutralization alters lung inflammation and leukocyte expression of CD80, CD86, and major histocompatibility complex class II in mice infected with Histoplasma capsulatum
Ja. Cain et Gs. Deepe, Interleukin-12 neutralization alters lung inflammation and leukocyte expression of CD80, CD86, and major histocompatibility complex class II in mice infected with Histoplasma capsulatum, INFEC IMMUN, 68(4), 2000, pp. 2069-2076
Histoplasma capsulatum induces a cell-mediated immune response in lungs and
lymphoid organs of mammals. Resolution of primary infection in mice depend
s on interleukin-12 (IL-12), since neutralization of this monokine increase
s susceptibility to infection. The present study was designed to determine
if blockade of IL-12 disrupts the protective immune response by altering th
e influx of lineage-specific cells into infected lungs and the numbers of c
ells expressing CD80, CD86, CD119, and major histocompatibility complex cla
ss II (MHC II) molecules. In mice given anti-IL-12, there was a 2.5-fold de
crease in total numbers of T cells on days 3 to 10 of infection and a 4-fol
d increase in Mac-1/Gr-1(+) cells on days 7 and 10 compared to infected con
trols. CD80(+) lung cells from anti-IL-12-treated mice were 2- to 3-fold gr
eater than those from controls on days 7 and 10, whereas the total numbers
of CD86(+) cells were 2- to 3 fold less and MHC II+ cells were 1.5- to 2-fo
ld less on days 3 and 5, Cells expressing CD119 were reduced 1.5-fold on da
y 5. Treatment with monoclonal antibodies (MAb) to CD80, CD86, or both redu
ced the fungal burden slightly compared to that in rat immunoglobulin G-tre
ated controls, whereas after IL-12 neutralization, blocking of CD80 reduced
the tissue burden by 2.5-fold and this correlated with a decrease in IL-4.
Regardless, mortality was not altered by treatment with MAb to CD80 or CD8
6. We conclude that (i) IL-12 neutralization alters the nature of the infla
mmatory response in lungs and the expression of CD80 and CD86 on lineage-sp
ecific cells, (ii) the immune response during infection with H. capsulatum
is controlled via mechanisms independent of the CD80 and CD86 costimulatory
pathways, and (iii) decreased expression of CD86 and MHC II may modulate g
eneration of optimal protective immunity.