**5. Conclusion and future directions**

After receiving three stimulation signals from APCs, naïve CD4+ T cells differentiate into effector subtypes such as Th1, Th2, and Th0 cells. While clear-cut Th1 and Th2 are the common subtypes detected in mice and humans, hybrid Th0 is common in cattle infected by both intracellular and extracellular pathogens. In fact, Th0 responses induced in many bovine diseases might consist of a mixed population of Th1, Th2, and Th0 subtypes. Thus, despite similarities in general, bovine CD4+ T cell responses seem to be partially different from the Th1/Th2 responses classically defined in mice and humans. Therefore, understanding the mechanisms of bovine CD4+ T cell differentiation and its regulation by pathogens may facilitate the development of more effective vaccines and designing immune intervention strategies against important chronic bovine infectious diseases.
