Immunomodulation of Delayed-Type Hypersensitivity Responses by Mesenchymal Stem Cells Is Associated with Bystander T Cell Apoptosis in the Draining Lymph Node.

(Lim et al. J Immunol) Immune responses are quantified in many ways. Typically one thinks about immunity as the ability of an organism to overcome infection with another organism. However this test is impossible to perform in a reproducible, quantitative, and ethical way in humans. An alternative test was developed by immunologists called delayed type hypersensitivity (DTH) reaction. In this assay the patient is immunized with an antigen and subsequently the antigen is painted on the skin. The T cells that recognize the antigen then home to the skin, activate macrophages, which in term produce a swelling reaction that can be visualized easily.

Mesenchymal stem cells (MSC) have been described to be immune modulatory, however to our knowledge this is the first publication in which effects of MSC on DTH were examined.

In this paper the authors reported that subsequent to induction of a DTH response in which MSC were administered to the host, a small but significant number of MSCs accumulate in the secondary lymphoid organs and attenuate delayed-type hypersensitivity (DTH) response by inducing apoptotic cell death of surrounding immune cells in the draining lymph node (LN).

In order to visualize killing of immune system cells by the administered MSC, the scientists administered fluorescently-labeled MSC intravenously in mice after initiation of DTH. They observed that MSC preferentially accumulated at the boundary between the paracortical area and the germinal center in the lymph nodes, in close proximity to various types of immune cells including T, B, and dendritic cells in a dose-dependent manner.

It was reported that accumulated MSCs markedly attenuated DTH response in proportion to the number of MSCs infused. During the DTH response, the infiltration of T cells in the challenged site was significantly decreased, whereas a number of apoptotic T cells were remarkably increased in the draining lymph node.

Killing of immune cells seemed to be restricted to activated T cells since apoptosis was observed only in the BrdU stained (proliferating) cells. Additionally it appeared that T cell death was mediated by MSC secretion of nitric oxide.

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