Abstract
T cell-mediated immunity plays a prominent role in combating pathogens infection. Both the engagement of the T cell receptor with the peptide-bound major histocompatibility complex and a costimulatory signal are needed for the complete activation of the T cell. To determine whether host immune responses to vaccination could be improved by enhancing CD28-mediated costimulation and verify whether the boosted immune responses could protect the host against viral challenge, we produced a transgenic pig line expressing an extra copy of the CD28 gene controlled by its own promoter at the Rosa26 locus. As expected, in response to porcine reproductive and respiratory syndrome virus (PRRSV) strain vaccination, CD4+ T cells was remarkably increased in CD28 transgenic pigs and a similar response in CD8+ T cells was elicited after challenge. Importantly, because of increased T cell frequencies, the virus-neutralizing antibody against JXA-1 (a highly pathogenic Chinese PRRSV strain), as well as interferon-γ secretion, were enhanced in transgenic pigs. These findings in our translational study provide a novel concept for farm animal breeding in disease resistance, in which we may use the transgenic technology to force overexpression of confirmed immunity-promoting molecules like CD28 and produce an animal with enhanced immune responses to vaccination and broad-spectrum resistance to infectious diseases.
Highlights
There is growing evidence that T cells are central effectors for adaptive immune responses, which help protect the host against pathogens infection [1,2,3]
The results show that joint ligation of CD3 and CD28 with anti-CD3 plus anti-CD28 mAbs strongly synergized to phosphorylate the ERK1/2 kinase (Figure 2C), demonstrating that overexpression of CD28 contributed to the increase of phosphorylation events during T cell activation
We generated Tg pigs expressing an extra copy of CD28 and evaluated the effect of the enhanced costimulatory signaling on T cell responses following porcine reproductive and respiratory syndrome virus (PRRSV) vaccination and challenge
Summary
There is growing evidence that T cells are central effectors for adaptive immune responses, which help protect the host against pathogens infection [1,2,3]. Increased Immune Responses through CD28 interaction with the T cell receptor [2, 4, 5, 7, 8]. The other signal is delivered by the binding of costimulatory molecules to their ligands [2, 6, 7]. It is well known that signaling solely through the interaction of TCR with MHC–peptide complex results in anergy [9]. Costimulatory molecules, playing a key role in the modulation of T cell responses, are becoming promising candidates for immunotherapy [10]. CD28 provides a more robust costimulatory signal, which has been well documented in numerous studies [11,12,13]
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