SCRNAseq_CD4_T_memory. SCRNAseq_CD4_T_memory

Malaria, the disease caused by infection with protozoan parasites of genus Plasmodium, remains a leading cause of disease in developing countries. Despite extensive research efforts, we are still without an effective way of inducing long-term protection, either naturally or by vaccination. Results from the field and experimental models have implicated CD4+ T cells in providing protection against the blood stage of infection (Weiss, Sedegah et al. 1993, Whitworth, Morgan et al. 2000). After a primary infection, the pool of effector CD4+ T cells contracts (Buchholz, Schumacher et al. 2016), leaving only a fraction of cells as long-lasting memory cells (Schlub, Sun et al. 2011). The two classical memory subsets are effector memory cells (TEM; CD44hi, CD62Llo), which recirculate between peripheral tissues and the blood via the lymphatics and provide protective immunity, and central memory cells (TCM; CD44hi, CD62hi), which remain in secondary lymphoid tissue and provide reactive immunity. TCM and TEM cells have been identified in mouse models of malaria, and are likely important for providing long-term protection against this disease in humans (Migot, Chougnet et al. 1993, Stephens and Langhorne 2010). A significant question in the field has been whether a particular subset of effector cells is more likely give rise to memory cells. A recent study by Tubo et al. used limiting dilutions to transfer single antigen-specific CD4+ T cells into Listeria monocytogenes infected recipient mice. They then tracked the effector response of these cells and their transition into memory cells (Tubo, Fife et al. 2016). Their results showed that each T cell clone had memory potential and the helper phenotype of a clonal memory population roughly matched its effector phenotype. Remaining questions are when does an effector T cell commits to becoming a memory cells, what does this look like on the transcriptional level, do memory responses require continued presence of parasite antigen and are there any changes in the epigenome of the progenitors of these cells.