Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders

The intestinal immune system, which must ensure appropriate immune responses to both pathogens and commensal microflora, comprises innate lymphoid cells and various T-cell subsets, including intra-epithelial lymphocytes (IELs). An example of innate lymphoid cells is natural killer cells, which may be classified into tissue-resident, CD56(bright) NK-cells that serve a regulatory function and more mature, circulating CD56(dim) NK-cells with effector cytolytic properties. CD56(bright) NK-cells in the gastrointestinal tract give rise to indolent NK-cell enteropathy and lymphomatoid gastropathy, as well as the aggressive extranodal NK/T cell lymphoma, the latter following activation by EBV infection and neoplastic transformation. Conventional CD4+ TCR alpha beta+ and CD8 alpha beta+ TCR alpha beta+ T-cells are located in the lamina propria and the intraepithelial compartment of intestinal mucosa as type 'a' IELs. They are the putative cells of origin for CD4+ and CD8+ indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and intestinal T-cell lymphoma, NOS. In addition to such conventional T-cells, there are non-conventional T-cells in the intra-epithelial compartment that express CD8 alpha alpha and innate lymphoid cells that lack TCRs. The central feature of type 'b' IELs is the expression of CD8 alpha alpha homodimers, seen in monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), which primarily arises from both CD8 alpha alpha+ TCR alpha beta+ and CD8 alpha alpha+ TCR gamma delta+ IELs. EATL is the other epitheliotropic T-cell lymphoma in the GI tract, a subset of which arises from the expansion and reprograming of intracytoplasmic CD3+ innate lymphoid cells, driven by IL15 and mutations of the JAK-STAT pathway.

Automated summary

The intestinal immune system is made up of innate lymphoid cells and various T-cell subsets, which play important roles in immune responses and can also be involved in the development of lymphoma. Understanding the different cell types and their functions in the gastrointestinal tract is crucial for studying and treating related diseases.