CD4(-CELL-MEDIATED FATAL HYPERINFLAMMATORY REACTIONS IN MICE INFECTEDWITH PENICILLIUM-MARNEFFEI() T)

In the present study, we demonstrate that all mice survived when a low dose of Penicilliun marneffei was instilled intratracheally, while se vere infection induced by instillation of 1x10(8) and 1x10(7) colony-f orming units (CFU) killed all and 50% of mice, respectively, within 14 days, although the number of live microorganisms in the lungs of thes e animals was found to decrease with time. The cellular inflammatory r esponses in the lungs were much more striking in mice with severe infe ction than in animals infected with a low dose of microorganisms. The number of leucocytes, macrophages, neutrophils and lymphocytes in the lungs increased progressively during infection, and were more than 50 times higher on day 11 than in the control count. CD4(+) T cells were the predominant cells in the lungs, and played an important role in hy perinflammatory host reactions, because neutralizing anti-CD4 MoAb inc reased the survival rate in infected mice despite the presence of a hi gh number of Live microorganisms in the lungs. Our results indicate th at severe infection with P. marneffei induces fatal hyperinflammatory host reactions, mediated to a large extent by CD4(+) T cells, although the infection is well controlled. However, the contribution of endoge nous tumour necrosis factor-alpha (TNF-alpha) remains unsubstantiated, since administration of neutralizing anti-TNF-alpha MoAb in the prese nt study failed to prolong survival in infected mice.