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SUMMARYExtracorporeal photochemotherapy ( ECP) has been shown to be a potent activator of peripheral blood macrophages because it causes a marked release of macrophage-dependent proinflammatory cytokines, and it is therefore currently considered to be a safe and non-toxic immunomodulatory treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC ) in eight patients with early stage (Ib) cutaneous T-cell lymphoma (CTCL), before and 1 year after ECP, together with their clinical and histological responses. In particular we evaluated in vitro phytohaemagglutinin (PHA)-stimulated proliferation and production of interleukin-4 (IL-4) and interferon-c (IFN-c) as well as lipopolysaccharide (LPS)-induced production of IL-12. Before treatment we observed that PBMC of patients produced significantly higher levels of IL-4 and lower levels of IFN-c and IL-12 than those of healthy control subjects. After 1 year of ECP, IL-4, IFN-c and IL-12 production no longer differed from that of control subjects. Moreover, we observed a good clinical result matched by histological response. Our data confirm that earlystage CTCL patients show a predominantly type-2 immune response that might be responsible for several immunological abnormalities found in this disease. We have demonstrated that ECP reverses the T-helper type 1/T-helper type 2 (Th1/Th2) imbalance and may therefore be considered an efficient biological response modifier.

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Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first-and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-␥, transforming growth factor-␤1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third-than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age.

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