During infection with lymphocytic choriomeningitis virus, CD8+ T cells differentiate rapidly into effectors (CD62LlowCD44high) that differentiate further into the central memory phenotype (CD62LhighCD44high) gradually. To evaluate whether this CD8+ T cell differentiation program operates in all infection models, we evaluated CD8+ T cell differentiation during infection of mice with recombinant intracellular bacteria, Listeria monocytogenes (LM) and Mycobacterium bovis (BCG), expressing OVA. We report that CD8+ T cells primed during infection with the attenuated pathogen BCG-OVA differentiated primarily into the central subset that correlated to reduced attrition of the primed cells subsequently. CD8+ T cells induced by LM-OVA also differentiated into central phenotype cells first, but the cells rapidly converted into effectors in contrast to BCG-OVA. Memory CD8+ T cells induced by both LM-OVA as well as BCG-OVA were functional in that they produced cytokines and proliferated extensively in response to antigenic stimulation after adoptive transfer. During LM-OVA infection, if CD8+ T cells were guided to compete for access to APCs, then they received reduced stimulation that was associated with increased differentiation into the central subset and reduced attrition subsequently. Similar effect was observed when CD8+ T cells encountered APCs selectively during the waning phase of LM-OVA infection. Taken together, our results indicate that the potency of the pathogen can influence the differentiation and fate of CD8+ T cells enormously, and the extent of attrition of primed CD8+ T cells correlates inversely to the early differentiation of CD8+ T cells primarily into the central CD8+ T cell subset.

Syk kinase is best known as a critical component of immunoreceptor signaling in leukocytes. Activation of Syk following cross-linking of Fcgamma and Fcepsilon receptors on macrophages, mast cells, and other cells induces various inflammatory events. We hypothesized that Syk is involved in inflammatory responses induced by the lipopolysaccharide (LPS). We studied the role of Syk using its inhibition by antisense oligonucleotides, or small interfering RNA. Our data demonstrated that in vivo inhibition of Syk caused down-regulation of LPS-induced responses in rat alveolar macrophages. In in vitro experiments, inhibition of Syk in rat peritoneal macrophages, as well as in human myelomonocyte cell line THP-1 also caused a decrease in LPS-induced cytokine release. Our data support the hypothesis that, in macrophages, Syk is involved in LPS-induced intracellular signaling pathways leading to the release of pro-inflammatory mediators. Understanding the role of Syk in LPS-induced signaling may help in developing new therapeutic tools for inflammatory disorders.