Objective To test the hypothesis that the formation of ectopic germinal center (GC)–like structures in Sjögren's syndrome (SS) is associated with the ectopic expression of the constitutive lymphoid tissue–homing chemokines B cell–attracting chemokine 1 (BCA‐1; or, CXCL13) and stromal cell–derived factor 1 (SDF‐1; or, CXCL12). Methods Immunohistochemical and immunofluorescence analysis was used to determine the expression of the constitutive chemokines BCA‐1 (CXCL13) and SDF‐1 (CXCL12) in salivary glands from 5 SS patients and 3 non‐SS patients. In addition, the expression of their respective receptors (CXCR5 and CXCR4) was examined on infiltrating lymphocytes. Human tonsil was used as a positive control for secondary lymphoid tissue. Results BCA‐1 (CXCL13) was expressed within lymphoid aggregates in SS, which shared many structural features with GCs in tonsil. BCA‐1 (CXCL13) was completely absent in control biopsy samples from patients who did not have SS. High levels of BCA‐1 (CXCL13) were also found on endothelial cells in salivary glands from SS patients. Diseased SS tissue was infiltrated by CXCR5‐expressing B cells which organized into GC‐like clusters. In complete contrast, SDF‐1 (CXCL12), a constitutive chemokine involved in leukocyte retention within lymphoid tissue, was expressed by epithelial cells in both diseased and control samples. The chemokine receptor for SDF‐1, CXCR4, was expressed on T cells that accumulated in a periductal distribution in diseased tissue. Conclusion The ectopic expression of BCA‐1 (CXCL13) on endothelial cells and within GC‐like structures, together with the strong expression of SDF‐1 (CXCL12) on ductal epithelial cells, is a unique feature of inflamed glands in SS. By creating a local microenvironment supportive of focal B cell aggregation and differentiation, with structural features that are remarkably similar to GCs, BCA‐1 (CXCL13) and SDF‐1 (CXCL12) may contribute to the excessive production of high‐affinity, class‐switched autoantibodies and to the high incidence of B cell lymphomas classically associated with SS.

Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.

We conclude that this antibody is potentially a useful positive marker for the identification of the epithelioid variant of mesothelioma in formalin-fixed and paraffin-embedded material.

No abstract

Persistence of human immunodeficiency virus (HIV) in a latent state in long-lived CD4+ T-cells is a major barrier to eradication. Latency-reversing agents that induce direct or immune-mediated cell death upon reactivation of HIV are a possible solution. However, clearance of reactivated cells may require immunotherapeutic agents that are fine-tuned to detect viral antigens when expressed at low levels. We tested the antiviral efficacy of immune-mobilizing monoclonal T-cell receptors against viruses (ImmTAVs), bispecific molecules that redirect CD8+ T-cells to kill HIV-infected CD4+ T-cells. T-cell receptors specific for an immunodominant Gag epitope, SL9, and its escape variants were engineered to achieve supraphysiological affinity and fused to a humanised CD3-specific single chain antibody fragment. Ex vivo polyclonal CD8+ T-cells were efficiently redirected by immune-mobilising monoclonal T-cell receptors against viruses to eliminate CD4+ T-cells from human histocompatibility leukocyte antigen (HLA)-A*0201-positive antiretroviral therapy-treated patients after reactivation of inducible HIV in vitro. The efficiency of infected cell elimination correlated with HIV Gag expression. Immune-mobilising monoclonal T-cell receptors against viruses have potential as a therapy to facilitate clearance of reactivated HIV reservoir cells.