AG-011

The pleiotropic cytokine interleukin (IL)-10 is best characterized by its ability to downregulate inflammation and promote peripheral tolerance. On the other hand, IL-10 was also found to maintain the effector response of CD8⁺ T cells and promote the expansion of tumor-resident CD8⁺ T cells. In diffuse large B cell lymphoma (DLBCL), the role of IL-10 has been characterized in tumor cells but not in CD8⁺ T cells. We found that CD8⁺ T cells in DLBCL presented robust interferon (IFN)-γ expression early during TCR-activation but could not maintain this response later on, which was characterized by significantly lower CD8⁺ T cell degranulation and higher apoptosis. These observations were associated with higher PD-1 expression in DLBCL CD8⁺ T cells. Furthermore, the PD-1⁺ cells were strongly enriched in the IFN-γ⁺, but not the IFN-γ^-, fraction. Interestingly, exogenous IL-10 significantly improved the survival of DLBCL CD8⁺ T cells, and resulted in significantly higher IFN-γ, ganzyme A and granzyme B expression in the absence of CD19⁺ tumor cells, and significantly improved CD8⁺ T cell-mediated specific lysis of CD19⁺ tumor cells. IL-10 did not alter the expression of PD-1 in DLBCL CD8⁺ T cells, but curiously, IL-10-treated DLBCL CD8⁺ T cells were less susceptible to PD-L1-mediated apoptosis. We then demonstrated that IL-10 treatment significantly elevated the expression of pro-survival factor Bcl-2. Blocking IL-10 resulted in higher apoptosis, fewer IFN-γ⁺ CD8⁺ T cells, and lower Bcl-2 expression. IL-10 also significantly increased STAT3, but not STAT1, phosphorylation in CD8⁺ T cells. Together, these results suggested that IL-10 could enhance CD8⁺ T cell inflammation in DLBCL patients.

In an effort to identify the Rhizoctonia spp. associated with seedling diseases of soybean, Rhizoctonia isolates were recovered from soybean seedlings with damping off and root and hypocotyl rot symptoms from Arkansas, Illinois, Kansas, Michigan, Minnesota, and the Canadian province of Ontario between 2012 and 2014. Based on cultural morphology, polymerase chain reaction restriction fragment length polymorphism, and phylogenetic analysis of the internal transcribed spacer (ITS) region of the ribosomal RNA genes, 80 isolates were confirmed to be Rhizoctonia solani, 24 were binucleate Rhizoctonia spp., and 10 were R. zeae. Of the 80 R. solani isolates, one belonged to anastomosis group (AG) 2-1, 52 belonged to AG-2-2IIIB, five belonged to AG-3 PT, three belonged to AG-4 HGI, two belonged to AG-4 HGIII, nine belonged to AG-7, and eight belonged to AG-11. Bayesian inference of phylogeny using the ITS region revealed two clades of R. solani AG-7 that possibly correspond to different AG-7 subgroups. Phylogenetic analysis also provided evidence for genetic relatedness between certain binucleate Rhizoctonia and some R. solani isolates. On ‘Williams 82’ soybean, isolates of AG-2-2IIIB were the most aggressive, followed by isolates of AG-7, AG-4, and AG-11. On ‘Jubilee’, a sweet corn cultivar, AG-2-2IIIB and AG-4 isolates caused significant stunting and root damage, whereas the damage caused by the AG-11 isolates was mostly restricted to the mesocotyl. Isolates of R. zeae and the binucleate Rhizoctonia spp. were not pathogenic on soybean or corn. Our results indicate that soybean and corn are hosts to the predominant and aggressive AG of R. solani, implying that rotation between these two crops may not be an effective management practice.