CD4+ T cells play key roles in coordinating immune responses by producing molecules critical for the production of high affinity antibodies by B cells, helping to fully activate CD8+ T cells so they can kill infected and transformed cells, as well as assisting innate immune cells to recognize and kill pathogens. Hence, they play vital roles in generating anti-parasitic immunity, as well as in immune surveillance following resolution of infection. However, CD4+ T cell functions are often suppressed following parasite infection, leading to the development of disease. We identified several important immune regulators that impact on the generation of antigen-specific CD4+ T cells responses in experimental models of parasite infection, as well as in humans infected with the same pathogens. These include type I interferons (IFN’s) that are usually associated with the generation of effective anti-viral immunity. In experimental malaria and leishmania infections, this family of cytokines suppressed the development of parasite-specific CD4+ T cell responses via actions on dendritic cells. Blockade of type I IFN signalling pathways dramatically enhanced CD4+ T cell activation following infection, resulting in significantly improved control of parasite growth and reduced disease. The mechanisms by which type I IFN’s influence CD4+ T cell activation will be discussed, as well as how this knowledge can be used to develop new strategies for vaccination and treatment of infectious diseases.
Grant funding provided by the Australia NHMRC and The Australia-India Strategic Research Fund.