Action of Dexamethasone in the Suppression of Delayed-type Hypersensitivity in Reconstituted SCID Mice

Objective And Design: It is not known whether the amelioration of inflammation by corticosteroids is mediated through a direct effect on the T cells or by effects on other inflammatory cells and/or their products. To explore the mechanisms whereby corticosteroids exert their effects on T cell dependent inflammation we have used severe combined immunodeficiency (SCID) mice. These mice are largely devoid of functional T and B lymphocytes, hence being unable to raise delayed type hypersensitivity (DTH), but display intact antigen presenting capacity. The aim of this study was to analyse the target cell population participating in DTH and being affected by corticosteroid treatment.

Materials And Methods: SCID mice were reconstituted with naive thymocytes from congeneic C.B-17 mice. The day after cell transfer, recipient SCID mice were sensitised by epicutaneous application with oxazolone (OXA). One week later all the mice were challenged with OXA and DTH reaction was registered. Recipient SCID mice were administered a single dose of Dexamethasone (Dex) either one day before cell transfer or one day before the challenge. A group of donor mice was treated with Dex prior to cell preparation for transfer. Also intact C57B1/6 (B6) mice were treated with corticosteroids either before sensitisation or before challenge.

Results: In B6 mice, a single injection of Dex significantly decreased DTH when given one day before challenge but had no effect when given one day before sensitisation. In SCID mice treated with various doses of Dex one day before challenge, a profound depression (P < 0.01-0.001) of DTH reactivity was observed, compared to controls. In contrast, administration of Dex to recipient SCID mice before cell transfer resulted in an increased rather than decreased DTH response among SCID recipients. SCID mice receiving Dex exposed thymocytes displayed no significant differences in DTH response, compared to the controls.

Conclusions: Our results indicate that corticosteroids exert suppressive impact on the effector phase of DTH response in mice by anti-inflammatory properties of the hormone or by effects on OXA-sensitised memory T cells.