Terminal Differentiation of Regulatory T Cells a Crucial Step to Developing an Effective Therapy for Intestinal Inflammation

The T cell represents a very important class of lymphocytic cells involved in cell-mediated immunity. Members of this group include the CD4+ and CD8+ cells which have been proven to act as the controllers and effectors of immune response respectively. While the helper T cell (which forms one class of CD4+ cells) is involved in controlling immune responses by exaggerating that response, the regulatory T cell (another member of this family) controls immune responses by suppressing and even halting that response altogether. The T cells are mostly found in lymphoid tissues including the spleen and lymph nodes; however, there is growing evidence that Treg cells also exist in non-lymphoid tissues such as among the gut flora in the intestinal mucosa. Recent studies show that certain adaptations of the Treg cells upon activation allow them to perform their immunosuppressive and tissue supportive functions while coexisting with other cells of the non-lymphoid tissues; However, scientists have been puzzled about the nature of these adaptations and mechanisms by which they are developed. Are these adaptations a result of stable differentiation of the Treg cells upon activation, or can they be said to be activation states which can be reversed to deactivate the Treg?

T Cell

T Cell

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Scientists at Memorial Sloan Kettering Cancer Center have associated these adaptations exhibited in activated Treg cells with the terminal differentiation of the cells.

The mechanism by which T cells acquire terminal differentiation

The mechanism of differentiation of T cells is one that has been studied by various scientists. While there are slight differences between these postulations, a common denominator to these mechanisms is the fact that Treg differentiates upon antigen-induced activation and expresses features that are well suited for their immunosuppressive roles.

The result of this research however discovered a subset of Treg cells distinguished by stable expression of interleukin-10. These cells were formed following the terminal differentiation of the activated T cells.

Animal studies carried out following this discovery further elucidated their role in preventing autoimmune diseases in non-lymphoid tissues among other functions.

Clinical significance

The existence of Treg cells among the numerous microorganisms in the gut wall is a useful tool for the prevention of autoimmune responses in the gut. By maintaining self-tolerance, these cells prevent host cytotoxic T cells from damaging other host cells. Although this function has been exploited since the discovery of the Treg cells in the early 1970s, effective exploitation of this function has eluded clinicians; However, by truly understanding these underlying mechanisms responsible for the actions of the regulatory T cells, we can successfully harness these functions.

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Since we now know that T cell subsets obtained after the terminal differentiation of the naive T cells were most crucial to preventing exaggerated inflammatory responses, we can apply these findings to develop an effective therapy for autoimmune diseases, especially those occurring due to autoimmune reactions in non-lymphoid tissues.

Immunotherapy for diseases such as ulcerative colitis and other autoimmune diseases of the gut flora could be easily developed.


These findings are proof of the ever-expanding science of immunochemistry and its innumerable applications in developing an effective therapy for several diseases which plague humankind. They would also form a framework upon which further research would be carried out.

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Terminal differentiation and persistence of effector regulatory T cells essential for the prevention of intestinal inflammation




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