Tu134 - High CD96 Expression Marks an IL-22 Producing CD4 T cell Population Reduced in Lupus Patients

Systemic lupus erythematosus (SLE) is an autoimmune disease that remains an important diagnostic and therapeutic challenge. Manipulation of activating or inhibitory receptors on T cells represents a promising therapeutic strategy in diseases such as SLE. Our goal is to define patterns of immunomodulatory receptor expression on T cells and to identify alterations in immunomodulatory receptor expression on T cells in patients with SLE.

Method: We analyzed PBMC from SLE patients and controls (n=20 each) with a 35-markers mass cytometry panel. To identify subpopulations altered in SLE, we used FlowSOM to evaluate memory CD4+ T cells in a multidimensional manner. We compared the abundances of the metaclusters in SLE and control samples. Next, we performed low-input bulk RNA-seq to characterize the altered populations. We validated RNA-seq results by flow cytometry. Result: We identified a CD4 population that is decreased in frequency in SLE patients and marked by high expression of CD96 (and lack of PD-1 and TIGIT). RNA-seq analysis revealed that the CD96 population highly expressed CCR6, RORA, IL-22, IL-2, oncostatin M and is enriched for a Th22, not Th17 transcriptomic signature. Functional in vitro stimulation experiments demonstrated that CD96+ T cells comprise a population that is preferentially enriched for IL-22, with intermediate capacity for IL-17A and IFN-gamma production.Conclusion: We have identified a population represented by high expression of CD96 that is reduced in frequency in PBMC of SLE patients, with high capacity for IL-22. Mechanisms involved in the depletion of this population in SLE are currently being investigated.