In addition, we use minigenes to induce protective immunity, and we are developing methods to increase the immunogenicity of weakly immunogenic sequences, thereby expanding the vaccine universe. Finally, in studies with R. Fujinami, University of Utah, and M. von Herrath, Department of Neuropharmacology, we are evaluating the usefulness of DNA immunization in altering the course of autoimmune disease. Cytotoxic T lymphocytes lyse infected targets and also can counter viral infection by secreting antiviral cytokines. However, cytokine production is turned on within minutes after the cells encounter the appropriate antigenic stimulus. Remarkably, if the contact between T cells and antigen-presenting cells is disrupted, cytokine production ceases instantly, but production restarts immediately upon restoration of the antigenic stimulus.
Cytokines are potentially toxic molecules and can even be lethal.
It is strongly implicated as an underlying cause of idiopathic dilated cardiomyopathy, the most common indicator for heart transplantation in young males. Recently, we showed that the virus exploits B lymphocytes, using them as Trojan horses to accelerate viral dissemination. We also found that the tropism of coxsackievirus B3 for the acinar cells of the exocrine pancreas is related to the expression of the proposed receptor for the virus. We are evaluating DNA immunization in the coxsackievirus B3 model and are constructing recombinant coxsackieviruses to more precisely understand the immunologic and immunopathologic characteristics associated with this infection. Antisense approaches, which rely on the uniqueness of the viral nucleic acid sequence, offer a tantalizing alternative approach to antiviral therapy.