| First Author | Shi M | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 3 | Pages | 1724-32 |
| PubMed ID | 16424202 | Mgi Jnum | J:126643 |
| Mgi Id | MGI:3761774 | Doi | 10.4049/jimmunol.176.3.1724 |
| Citation | Shi M, et al. (2006) Experimental African trypanosomiasis: a subset of pathogenic, IFN-gamma-producing, MHC class II-restricted CD4+ T cells mediates early mortality in highly susceptible mice. J Immunol 176(3):1724-32 |
| abstractText | Infections of highly susceptible BALB/c mice with virulent strains of Trypanosoma congolense or Trypanosoma brucei result in rapid death (8 days). We have previously shown that this mortality is IFN-gamma dependent. In this study we show that IFN-gamma is produced predominantly by CD3+Thy1.2+TCRbeta+CD4+ T cells shortly before the death of infected mice. Mortality may therefore be dependent on IFN-gamma-producing CD4+ T cells. Surprisingly, infected CD4+/+ and CD4-/- BALB/c mice have similar parasitemia and survival time. In infected CD4-/- mice, the production of both IFN-gamma and IL-10 is very low, suggesting that both cytokines are predominantly produced by CD4+ T cells and that the outcome of the disease might depend on the balance of their effects. Infected BALB/c mice partially depleted of CD4+ T cells or MHC class II function have lower parasitemia and survive significantly longer than infected normal BALB/c mice or infected BALB/c mice whose CD4+ T cells are fully depleted. Partial depletion of CD4+ T cells markedly reduces IFN-gamma secretion without a major effect on the production of IL-10 and parasite-specific IgG2a Abs. Based on our previous and current data, we conclude that a subset of a pathogenic, MHC class II-restricted CD4+ T cells (Tp cells), activated during the course of T. congolense infection, mediates early mortality in infected BALB/c mice via excessive synthesis of IFN-gamma. IFN-gamma, in turn, exerts its pathological effect by enhancing the cytokine release syndrome of the macrophage system activated by the phagocytosis of parasites. We speculate that IL-10-producing CD4+ T cells might counteract this effect. |
