RESUMEN
A regulatory function for CD4 molecules in lymphocyte adhesion and motility was investigated. Murine splenic CD4+ T cells, activated in the presence of phorbol ester and immobilized anti-CD4 mAb, adhered to the plastic surface and formed extended cytoplasmic projections (pseudopodia). Pseudopod formation was cell-density-dependent, peaked at Day 3, and disappeared by Day 5 in culture. This response could be inhibited by soluble anti-CD4 and by RGD-containing peptide. Ligation of CD4 was required at a late stage in cell activation, and stimulated cell motility in vitro. Addition of IL-4, but not IL-2, upregulated pseudopod formation induced by suboptimal stimuli. Anti-IL-4 mAb blocked pseudopod formation, and exogenous IL-4 restored the response. A combination of IL-4 plus phorbol ester, but not IL-2 plus phorbol ester, induced pseudopod formation in concert with CD4 ligation. Exogenous IL-2, on the other hand, blocked pseudopod formation. CD45RBlow CD4+ T cells were much more efficient than CD45RBhigh CD4+ T cells for pseudopod formation. These results indicate that CD4 ligation induces CD4+ T-cell adhesion and motility, mainly in the memory/activated subset, which might be relevant for immune responses in vivo.
Asunto(s)
Antígenos CD4/inmunología , Linfocitos T CD4-Positivos/inmunología , Adhesión Celular , Seudópodos , Animales , Recuento de Células , Movimiento Celular , Células Cultivadas , Memoria Inmunológica , Interleucina-4/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Bazo/citología , Bazo/inmunologíaRESUMEN
Alterations to lymphocyte subsets in the thymus and spleen of rabies-infected mice were investigated in a kinetic study covering the entire course of infection. Changes in the levels of thymic Thy1.2 cells were found to be proportional to total thymocyte depletion, while thymic CD4-/CD8- and B cell subsets were observed to increase in comparison to the total number of cells. The same was found to be true of CD4 and CD8 thymocytes, but only after the first clinical signs of disease had appeared. Meanwhile, drastic reductions in the number of CD4+/CD8+ thymocytes occurred during the course of infection. In the spleen, on the other hand, alterations to splenocyte subsets were not selective. Thymocytes expressing high levels of CD4 or CD8 markers were detected shortly before the death of the animals. Following the appearance of rabies symptomatology, lymphocyte proliferation decreased in comparison to the control. Thus, our results demonstrate that the thymus is the most injured lymphoid organ in cases of murine rabies infection.
Asunto(s)
División Celular/efectos de los fármacos , Mitógenos/farmacología , Rabia/inmunología , Subgrupos de Linfocitos T/patología , Animales , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Concanavalina A/farmacología , Femenino , Lipopolisacáridos/farmacología , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Fitohemaglutininas/farmacología , Bazo/inmunología , Bazo/patología , Timo/inmunología , Timo/patología , Factores de TiempoRESUMEN
Suckling mouse brain (SMB) rabies vaccine is the preparation most widely used in the countries of Latin American and the Caribbean. This vaccine, prepared according to the Fuenzalida and Palacios method, consists of three fixed rabies virus strains (CVS, 51, and 91). However, the World Health Organization recommends that rabies vaccines for human use be prepared using only a single strain of this virus. In order to determine whether any one of the antigens of the SMB vaccine could be eliminated from the preparation, the immunogenic capacity of the standard trivalent SMB vaccine was compared with that of experimental bivalent (CVS-51, CVS-91, and 51-91) and monovalent (CVS, 51, and 91) SMB vaccines. The study was conducted using adult and suckling albino mice provided by the laboratory at the Pan American Zoonoses Center, Buenos Aires, Argentina, and different strains of fixed and street rabies virus. The experimental vaccines were prepared using the Fuenzalida-Palacios method. Potency and cross-immunity tests were conducted. The results showed that the trivalent vaccine was the most effective in protecting the mice against both fixed and street rabies virus infections and also in inducing rapid development of neutralizing antibody at high titers.