CD8(+)-T-cell depletion ameliorates circulatory shock in Plasmodium berghei-infected mice

The Plasmodium berghei-infected mouse model is a well-recognized model for human cerebral malaria. Mice infected with P. berghei exhibit (i) metabolic acidosis (pH < 7.3) associated with elevated plasma lactate concentrations , (ii) significant (P < 0.05) vascular leakage in their lungs, hearts, kidn eys, and brains, (ii) significantly (P < 0.05) higher cell and serum glutam ate concentrations, and (iv) significantly (P < 0.05) lower mean arterial b lood pressures. Because these complications are similar to those of septic shock, the simplest interpretation of these findings is that the mice devel op shock brought on by the P. berghei infection. To determine whether the i mmune system and specifically CD8(+) T cells mediate the key features of sh ock during P. berghei malaria, we depleted CD8(+) T cells by monoclonal ant ibody (mAb) treatment and assessed the complications of malarial shock. P. berghei-infected mice depleted of CD8(+) T cells by mAb treatment had signi ficantly reduced vascular leakage in their hearts, brains, lungs, and kidne ys compared with infected controls treated with rat immunoglobulin G. CD8-d epleted mice were significantly (P < 0.05) protected from lactic acidosis, glutamate buildup, and diminished HCO3- levels. Although the blood pressure decreased in anti-CD8 mAb-treated mice infected with P. berghei, the cardi ac output, as assessed by echocardiography, was similar to that of uninfect ed control mice. Collectively, our results indicate that (i) pathogenesis s imilar to septic shock occurs during experimental P. berghei malaria, (ii) respiratory distress with lactic acidosis occurs during P, berghei malaria, and (iii) most components of circulatory shock are ameliorated by depletio n of CD8(+) T cells.