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Factor Expressed on Regulatory T Cells Keeps Autoimmunity in Check

Nov 2, 2016 12:42:11 PM / by Stacy Matthews Branch, DVM, PhD

One way that the immune system maintains self-tolerance is by a T-cell–mediated control of self-reactive cytotoxic T cells.Autoimmune disorders develop when the body’s immune system does not distinguish between the body’s own cells and antigens. The destruction by the immune system of normal tissues is the basis of autoimmune diseases. The search for effective treatments or cures for autoimmune disorders depends on understanding the factors involved in immune cell function.

Immunologic self-tolerance is the immune system’s means of distinguishing self from non-self. One way that the immune system maintains self-tolerance is by a T-cell–mediated control of self-reactive cytotoxic T cells. T cell populations important in this control are CD4+CD25+ T cells. Elimination of CD4+CD25+ T cells in mice leads to a number of autoimmune diseases but can also lead to enhanced tumor immunity.

Results from a study in mice show that a factor present on CD4+CD25+ T cells may be responsible for these cells’ suppression of self-reactive cytotoxic T cells. This factor, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is expressed on activated T cells and plays an important role in immunologic self-tolerance. The results of the mouse study show that blocking the function of CTLA-4 normally active on CD4+CD25+ T cells can lead to autoimmune diseases.

In the study, mice were given three weekly injections of antibodies against CTLA-4, CD25, or a mixture of both. Mice treated only with high doses of antibodies against CTLA-4 developed various autoimmune disorders such as of the gastrointestinal tract, salivary glands, and ovaries. This occurred even though the CD4+CD25+ T cell levels did not decrease. Those given a low dose of antibodies against CD25 or the mixture had lower levels of autoimmune responses but decreases in the level of CD4+CD25+ T cells. Therefore, the same types of autoimmune diseases seen when CD4+CD25+ T cells are eliminated can be caused just by blocking the action of CTLA-4.

These results suggest that CTLA-4 is an important and key factor needed for the suppression of self-reactive cytotoxic T cells. Blocking CTLA-4 alone is enough to lead to the pathological changes seen with autoimmunity. The knowledge of this role of CTLA-4 can be used to develop new therapies for preventing or treating autoimmune disorders or even help find ways to enhance tumor cell immunity.

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Reference:
Takahashi, Takeshi et al. "Immunologic Self-Tolerance Maintained By CD251CD41 Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4". N.p., 2016. Web. 1 Nov. 2016.

Topics: Autoimmune Disorders, Cytotoxic T Cells, Regulatory T Cells

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