Viral Infection: A Potent Barrier to Transplantation Tolerance

Figure 4

Modulation of regulatory mechanisms by virus infection. Regulatory T cells play a crucial role in transplantation tolerance to allogeneic organs. Regulatory mechanisms that prevent immune attack on allogeneic tissues may be compromised in the setting of viral infection by at least two mechanisms. Release of inflammatory cytokines by virus-infected cells can prevent the differentiation of uncommitted naive CD4⁺ T cells into Tregs. Naive CD4⁺ T cells can differentiate into regulatory T cells in the presence of TGF-β. However, in the presence of TGF-β and proinflammatory cytokines such as IL-6, and perhaps IL-21, naive T cells can be skewed to turn into effector T cells such as the IL-17-producing TH17 cells. In a separate mechanism, release of cytokines such as IL-6 by infected APCs can render alloreactive effector cells refractory to suppression by regulatory T cells.