RESUMO
Efficient and quick reconstitution of T-cell compartments in lymphopenic patients is of great importance to prevent opportunistic infections, but remains difficult to achieve. Human T-cell proliferation in a T-cell-receptor (TCR)-independent manner is possible in vitro with superagonist anti-CD28 antibodies, and such molecules are therefore promising therapeutic tools. Here, we investigated the in vivo effects of superagonist anti-CD28 treatment on human developing and mature T cells, in the recently developed model of "human immune system" BALB/c Rag2(-/-)gammac(-/-) mice. Our results show that superagonist anti-CD28 treatment transiently induces a 7-fold increase in thymocyte numbers and up to 18-fold accumulation of mature thymocytes. The increased thymic production lead to transient accumulation of mature T cells in the periphery at the peak of treatment effect (day 6). In addition, long-term peripheral T-cell depletion was induced. Furthermore, the concomitant selective expansion and accumulation of suppressive CD4+CD25+FoxP3+ T cells was induced in a transient manner. Superagonist anti-CD28 therapy could therefore be of clinical interest in humans, both for beneficial effect on thymic T-cell production as well as regulatory T-cell accumulation.
Assuntos
Anticorpos Monoclonais/farmacologia , Antígenos CD28/imunologia , Proteínas de Ligação a DNA/deficiência , Linfócitos T Reguladores/imunologia , Linfócitos T/imunologia , Timo/imunologia , Animais , Anticorpos Monoclonais/imunologia , Diferenciação Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/imunologia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacosRESUMO
Walking track analysis is a widely accepted technique for functional evaluation after sciatic nerve repair in rats, but it is labour-intensive. In 2000, Bervar described a time-saving digitised static footprint analysis. In that study there were good correlations between the traditional sciatic function index (SFI) and the newly-developed static sciatic index (SSI) and static toe spread factor (TSF), respectively. Despite promising results, static footprint analysis is still not widely used. The present study was designed to validate it. After transection of the sciatic nerve, end-to-end repair was assessed using video recorded dynamic and static footprints in 45 Wistar rats. We found an even better correlation between the SFI and both the SSI and the static TSF. In conclusion, static footprint analysis is a time-saving and easy technique for accurate functional assessment of peripheral nerve regeneration in rats.