Plasticity in Adaptive Immunity

A notable feature of the current issue of Viral Immunology is the strong focus on adaptive immune responses. T and B cells comprise a key component of the immune system's ability to control infection by tailoring their response to the specific pathogen encountered. The plastic nature of adaptive immunity provides clinicians the opportunity to elicit or modify the response, which is the basis of vaccination and several therapeutic interventions. However, we still have much to learn about how adaptive immune responses are appropriately generated and regulated. One malleable facet of the adaptive response is the affinity of the T cells or antibodies that respond to a pathogen. In a very interesting report, Holbrook and colleagues have investigated the factors regulating the avidity of CD8⁺ effector T cell responses during respiratory virus infection. Their work builds on previous studies showing that the initial CD8⁺ T cell response to infection exhibits high avidity, but transitions to lower avidity as the response progresses. The authors now demonstrate that this avidity modulation is correlated with decreased lck expression and increased sensitivity to lck inhibitors. Their data suggest the possibility that tuning within select individual effectors is a previously unappreciated mechanism for the control of avidity in vivo. Another aspect of the adaptive immune response is the impact of prior infections on subsequent immune responsiveness. For example, sequential prime and challenge with mismatched influenza A viruses can elicit enhanced respiratory disease in mammals, including humans, and may impact the subsequent induction of immunity. Gauger et al. have addressed this issue by evaluating the ability of pigs suffering from vaccine associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the heterologous challenge virus inciting the VAERD. Their studies indicate that vaccinated pigs generated a robust humoral immune response and elevated local adaptive cytokine levels. Therefore, it appears that VAERD does not necessarily adversely affect the induction of an immune response to challenge with heterologous virus despite the severe clinical disease and underlying lung pathology.

Several articles in this issue of Viral Immunology address clinical questions related to the viruses responsible for hepatitis A, B, and C. Hao et al. have investigated the kinetics of Th17 cytokines during telbivudine therapy in patients with chronic hepatitis B. It is thought that Th17 cells and the secreting cytokines play an important role in the immune response and inflammation that are induced by hepatitis B virus (HBV). The authors show that telbivudine affects both viral load and inflammation (i.e., declines in circulating HBV and HBV-specific Th17 cells and IL-22 production), with important implications for our understanding of pathogenesis of HBV. Kourkounti et al. have investigated hepatitis A vaccination in HIV-infected patients with a view towards understanding which patients were most likely to respond to the vaccine. They report that successful vaccination is associated with CD4 T cell counts inasmuch as patients with counts greater than 500 cells/mm³ were over four times more likely to respond to the vaccine than patients with lower CD4 T cell counts. The numbers of other immune cells, or the administration of antiretroviral therapy, did not predict vaccine responsiveness. Ashraf and colleagues have analyzed P2X receptors in chronic hepatitis C virus (HCV) infections by analyzing transcript levels in peripheral blood mononuclear cells (PBMCs). P2X receptors act as damage sensors by binding the adenosine-5’triphosphate that is released in response to most pathological events. The authors' studies confirm the significant involvement of P2X receptors in activating the inflammatory immune responses mediated by PBMCs during chronic HCV infection. Chronic HCV infection is also a major problem for patients that are on maintenance hemodialysis. To better understand the relationship between dialysis and chronic HCV infection, Shiina and colleagues have compared the peripheral immune responses in dialysis patients. They show that chronic HCV infection has a significant impact on innate immunity, but that this occurs independently of hemodialysis.

Finally, one article in the current issue addresses the relationship between autophagy and apoptosis during viral infections. Using an ectromelia orthopoxvirus (EMV), Martyniszyn et al. definitively show that autophagy and apoptosis can co-occur in RAW 264.7 cells exposed to EMV. These data offer new insights into the relationship between autophagy and apoptosis in EMV-infected macrophages.

Taken together, the reports presented in the following pages considerably add to our understanding of immune responses following acute and chronic viral infections.