The effect of antigen presenting cells on the cytokine profiles of stable and reactional lepromatous leprosy patients

In View of varied reports on the Th1/Th2 paradigm in leprosy, we used a nov el real time (RT) fluorogenic reverse transcriptase based PCR (RT-PCR) to m easure cytokine expression in peripheral blood cells from lepromatous lepro sy patients with stable disease and those suffering from erythema nodosum l eprosum (ENL:Type II) reactions. To evaluate the role of accessory cells in Th cell differentiation, co-expression of Th cytokines interferon gamma (I FN gamma) and interleukin (IL) 4 and regulatory cytokines IL 10 and IL 12 w as compared in antigen stimulated peripheral blood mononuclear cells (PBMC) , cultures containing T cells reconstituted with autologous monocytes (MO) and cultures containing T cells reconstituted with autologous dendritic cel ls (DC). 7/8 stable lepromatous leprosy patients showed co-expression of bo th IFN gamma and IL 4, suggesting a Th0 or a combination of Th1 + Th2 subse ts in PBMC. The RT-PCR demonstrated that stable lepromatous patients and pa tients in ENL had significantly higher levels of IFN gamma mRNA molecules c ompared to IL 4. In fact, 5/8 ENL patients had undetectable levels of IL 4 mRNA, with a skewing of the cytokine response towards a Th1-like profile. C onsistent with this, IL 12p40 mRNA molecules were significantly higher in t he PBMC of ENL patients compared to stable lepromatous patients (P < 0.01). Reconstitution of purified T cells with autologous DC and MO from the stab le lepromatous group resulted in down regulation of IL 4 (P < 0.03 for DC a nd P < 0.02 for MO) and IL 10(P < 0.01 for DC and P < 0.02 for MO), and a c onsequent skewing towards a Th1 profile similar to that seen in ENL patient s. The fact that accessory cells could alter the cytokine profile in the re constituted cultures suggests that they may play a role in determining Th s ubset differentiation in chronic diseases, and may influence the immunologi cal stability of such diseases. (C) 2000 Elsevier Science B.V. All rights r eserved.