CD28, 4-1BBL and LIGHT and immunity to viral infections

Abstract

Co-stimulation is a crucial component in determining the outcome of T cell activation. Although much is known about the importance of co-stimulation in generating adaptive immunity, it is unclear as to the in vivo role of these co{u00AD}stimulatory molecules in influencing the outcome of acute viral infections such as influenza, ectromelia and vaccinia. This study attempted to investigate the physiological role of CD28 during acute viral infections such as those mentioned previously. In addition, the roles of CD28, 4-1BBL and LIGHT co-stimulatory molecules in the generation of CD8{u207A} T cell diversity during primary and secondary influenza virus infection were investigated.

CD28<superscript>-/- mice exhibited impaired primary and secondary NP{u207A}CD8{u207A} T cell responses to influenza virus infection. In contrast 4-1BBL<superscript>-/- and LIGHT-/- mice displayed very little change in the CD8{u207A} T cell response compared to wild-type C57BL/6 mice. These results indicate an important role for CD28 in TCR repertoire selection, and minor roles for 4-1BBL and LIGHT during both primary and secondary responses. In terms of anti-viral resistance, CD28<superscript>-/- mice were more resistant to primary influenza virus infection than wild-type C57BL/6 mice. Increased resistance was measured by lower percentage weight loss, increased survival and better viral control. The expression of type I interferons also differed from wild-type levels. The physiological relevance of CD28 during poxvirus infection was also investigated. However, due to problems pertaining to genetic contamination in the colony of CD28<superscript>-/- mice used, the data obtained was not reliable.

Overall, these studies have enhanced our knowledge regarding the mechanisms that govern TCR repertoire selection in response to influenza virus, as well as the dual nature CD28 has in regards to the overall outcome of influenza virus infection. Even though CD28 co-stimulation is necessary for the induction of a potent T cell response, it may be detrimental in certain situations where immunopathology is concerned. Show more