The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.
Bottom Line: The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response.So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host.The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype.
Affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.Show MeSH
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Mentions: Although our data above demonstrate the importance of T cells in the control of S. aureus infection, these cells did not succeed in clearing the infection. Therefore, we further investigated the mechanisms underlying the incomplete expression of T cell immunity. Under certain circumstances, sustained antigenic stimulation of T cells can lead to the development of a hyporesponsive state (Schwartz, 2003). Hence, we hypothesized that the permanent activation of T cells by the continuous presence of staphylococcal antigens during persistent infection may lead to immunological hyporesponsiveness. To corroborate this hypothesis, we determined the proliferative response of spleen cells isolated from mice at progressive times after bacterial inoculation to in vitro antigenic re-stimulation. Our results show that antigen-specific spleen T cells obtained from mice at day 7 p.i. responded to in vitro antigenic re-stimulation by active proliferation (Fig 9A). On the other hand, antigen-specific spleen T cells obtained from mice at >14 days p.i. became unresponsive to antigenic re-stimulation (Fig 9A). Spleen T cells isolated from S. aureus-infected mice during the persistent phase of infection were also hyporesponsive to stimulation with anti-CD3 along with the costimulatory signal provided by the anti-CD28 antibody (Fig 9B) or Concanavalin A (Con A; Fig 9C), which activate T cells in a TCR-mediated and antigen-presenting-cells-dependent manner. These results indicate that, with the transition from the acute to the persistent phase of staphylococcal infection, T cells entered a state of anergy.
Affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.