The aim of this experiment was to establish a mouse model of irradiation-in
duced oral candidiasis and to explore the cellular populations and mechanis
ms by which the infection is cleared from the oral mucosa. BALB/c mice rece
ived irradiation to the head and neck equivalent to 800 Rad using a Cobalt
60 gamma source. Both irradiated and non-irradiated mice were infected oral
ly with 1 X 10(8) Candida albicans yeasts. Compared with untreated controls
, irradiated animals developed a more severe infection of longer duration,
with hyphae penetrating the oral mucosa. Monoclonal antibody depletion of C
D4(+) but not CD8(+) T cells from the systemic circulation prolonged the in
fection in irradiated mice, but not in controls. Supernatants of submandibu
lar and superficial cervical lymph node cultures from irradiated animals de
monstrated significantly higher titers of interleukin-12, but similar level
s of interferon-gamma compared with controls. Screening for cytokine produc
tion by an RNase protection assay detected only macrophage migration inhibi
tion factor in irradiated and non-irradiated oral tissues from day 8 onward
s. The results of this study demonstrate a requirement for CD4(+) T cells i
n the recovery from oral candidiasis induced by head and neck irradiation i
n mice, and are consistent with a role for Th-1-type cytokines in host resi
stance.