03 December 2009

Genetically modified T-lymphocytes for arthritis therapy

Elena Novoselova, STRF.ru , based on the materials of Science-Business Exchange: Engineered antigen-specific Tregs for adaptive autoimmune disease therapyRegulatory T lymphocytes (Treg) are central regulators of the immune response.

Their main function is to control the strength and duration of the immune response through the regulation of the function of T–effector cells (T-helper and T-cytotoxic cells).

These cells express the transcription factor FoxP3, which regulates the genes responsible for the differentiation of T cells and the expression of cytokines and other factors involved in suppressing the immune response. Due to its ability to influence a wide range of immune responses, Treg is considered an ideal candidate for the treatment of autoimmune disorders.

The clinical potential of regulatory T-lymphocytes is limited by the complexity of their isolation. In addition, in autoimmune disorders, the potential antigen is not always known.

Specialists from University College London and the Dutch Cancer Institute tested the capabilities of antigen-specific Treg, created by retroviral gene transfer, for the treatment of arthritis. Since the action of Treg is based on suppressing the immune response of the body, that is, acting directly on the effector cells of the immune system, in this case identification of the initiating antigen is not required.

During the experiments, specialists using one of the retroviruses achieved the conversion of regulatory T-lymphocytes (CD4+) into antigen-specific ones by transferring the TCR gene (T-cell receptors) and co-transferring the TCR gene and the FoxP3 transcription factor. After the introduction of these genetically modified lymphocytes to model mice with antigen-induced arthritis, Treg constructs retained activity and the ability to specialize in relation to specific antigens. As a result, in the foci of rheumatoid inflammation, there was a decrease in the number of T-helper 17 (Th17) and destructive processes of bone tissue, which indicates a decrease in the autoimmune reaction of the body.

Thus, in this work, the researcher was able to create by genetic engineering an effective design for the production of antigen-specific regulatory T-lymphocytes capable of selectively inhibiting tissue damage in the absence of systemic immune suppression. This eliminates the need to identify antigens – modified Tregs themselves determine which antibodies they produce in response to the antigens present.

The next stage of the study will be the creation of genetically engineered structures specific to other autoimmune disorders and the evaluation of their effectiveness in animal models.

Portal "Eternal youth" http://vechnayamolodost.ru03.12.2009

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