| dc.description | Natural suppressor (NS) cells are characterized by their ability to suppress the response of lymphocytes to immunogenic and mitogenic stimuli in a non-specific manner without a requirement for priming or major histocompatibility complex restriction. NS cells are found in a number of lymphoid tissues, including adult bone marrow, neonatal spleen and the spleens of pregnant mice, as well as after cytoreductive procedures, such as total lymphoid irradiation and treatment with high dose cyclophosphamide (Cy). However, there is a great deal of controversy over the precise lineage and mode of action of NS cells. Therefore, this study was undertaken to elucidate and compare the lineage and mechanisms of action of naturally-occurring splenic pregnancy-associated NS (SPANS) cells and experimentally-induced splenic NS cells following high dose cyclophosphamide (Cy) treatment of mice. | en_US |
| dc.description | It was found that NS activity is mediated by several distinct suppressor cell populations coexisting in the spleen of Cy-treated mice and pregnant mice. Cy-spleen harbours NS cells belonging to T cell, B cell, and myeloid cell lineages, as well as a population of null NS cells. However, on a per cell basis, the most potent NS cells resident in Cy-spleen belong to the myeloid lineage, on the basis of MAC-1 expression. Pregnancy spleen, on the other hand, contains NS cells mainly belonging to an immature T cell lineage with a CD3$\sp+,$ $\alpha\beta$TCR$\sp+$, CD4$\sp-$, CD8$\sp-$, J11d.2$\sp+$, B220$\sp+$ phenotype, as well as a null NS cell population. These findings advance the conclusion that natural suppression defines an activity rather than a particular cell type. Although MAC-1$\sp+$ Cy-induced NS cells and SPANS cells are phenotypically distinct, both NS cell populations inhibit DNA synthesis and IL-2 production in mixed lymphocyte reactions (MLR). This immunosuppressive activity is mediated via the elaboration of soluble inhibitory factors. SPANS cells inhibit DNA synthesis in MLR via the elaboration of a transforming growth factor-$\beta$1-like molecule, whilst IL-2 production in MLR is inhibited through the production of a second, as yet unidentified, soluble factor. On the other hand, MAC-1$\sp+$ Cy-induced NS cell-mediated suppression of DNA synthesis in MLR is partially dependent on prostaglandin synthesis. However, most of the Cy-induced inhibitory activity appears to be mediated by a novel immunosuppressive cytokine. Although Cy-induced NS cells and SPANS cells differ with respect to phenotype and the nature of the immunosuppressive factors that they produce, the end-result of NS activity exerted by these cells appears to be very similar, namely the inhibition of IL-2 production and cellular proliferation in MLR. | en_US |
