Immunosuppressive antimetabolites inhibit induction of contact hypersensitivity while lymphoablative drugs also prevent its expression.

Contact hypersensitivity is one of the most common skin diseases and its pharmacological control is an important clinical issue. We investigated the control of contact hypersensitivity by immunosuppressive drugs administered during sensitization or challenge. Mycophenolate mofetil, methotrexate and 5-fluorouracil completely inhibited contact hypersensitivity when administered during sensitization whereas they did not decrease inflammatory reaction when administered during challenge.

Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8+ T cytotoxic 1 cells inducing keratinocyte apoptosis.

Contact hypersensitivity (CHS) is a T cell-mediated, Ag-specific skin inflammation induced by skin exposure to haptens in sensitized individuals. Th1/T cytotoxic 1 cells are effector cells of CHS, whereas Th2/T regulatory CD4(+) T cells have down-regulating properties. We have previously shown that CHS to 2,4-dinitrofluorobenzene is mediated by specific CD8(+) effector cells, whose cytolytic activity is mandatory for induction of skin inflammation.

Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay.

The popliteal lymph node (PLN) assay has been proposed as a tool to predict systemic autoimmune reactions induced by medicinal products and chemicals, the mechanisms of which are poorly understood. To determine whether PLN responses involved Th1 or Th2 cell control, or both, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analysed on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA by lymph node cells after injection into the hind footpad of C57 BL/6 mice. Streptozotocin induced a dramatic increase in IFN-gamma mRNA production, which correlated with PLN responses as evidenced by augmented weight and cellularity indices.

The popliteal lymph node response to streptozotocin is under type 1, MHC class-I restricted, CD8(+) T-cell control.

The popliteal lymph node (PLN) assay has been proposed to predict the 'autoimmunogenic' potential of xenobiotics. A better understanding of the processes involved in PLN responses is needed to establish the value of this assay for preclinical safety evaluation. In order to determine whether PLN responses involve CD4(+) or CD8(+) T-cells, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analyzed after injection into the hind footpad of C57 BL/6 mice and major histocompatibility complex (MHC) class I or II deficient mice.