02804nas a2200469   4500000000100000008004100001260001300042653001000055653000900065653002300074653001700097653001800114653001600132653003000148653001100178653002100189653001900210653001900229653001900248653002600267653001200293653001600305653002500321653001900346653002900365100002000394700001400414700001100428700001600439700001300455700001500468700001500483700001800498700002100516245013100537856007800668300001100746490000800757050001300765520154200778022001402320       2004                            d  c2004 Jan10aAdult10aAged10aBacterial Proteins10aCD56 Antigen10aChaperonin 6010aChaperonins10aCytotoxicity, Immunologic10aHumans10aInterferon-gamma10aInterleukin-1210aInterleukin-1310aInterleukin-1810aKiller Cells, Natural10aleprosy10aMiddle Aged10aMycobacterium leprae10aRNA, Messenger10aT-Lymphocytes, Cytotoxic1 aDe La Barrera S1 aFiniasz M1 aFink S1 aIlarregui J1 aAleman M1 aOlivares L1 aFranco M C1 aPizzariello G1 aCarmen Sasiain M00aNK cells modulate the cytotoxic activity generated by Mycobacterium leprae-hsp65 in leprosy patients: role of IL-18 and IL-13.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808925/pdf/cei0135-0105.pdf  a105-130 v135  aDELA20043 a<p>Protection against intracellular pathogens such as Mycobacterium leprae is critically dependent on the function of NK cells at early stages of the immune response and on Th1 cells at later stages. In the present report we evaluated the role of IL-18 and IL-13, two cytokines that can influence NK cell activity, in the generation of M. leprae-derived hsp65-cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) of leprosy patients. We demonstrated that IL-18 modulates hsp65-induced CTL generation and collaborates with IL-12 for this effect. In paucibacillary (PB) patients and normal controls (N) depletion of NK cells reduces the cytolytic activity. Under these conditions, IL-12 cannot up-regulate this CTL generation, while, in contrast, IL-18 increases the cytotoxic activity both in the presence or absence of NK cells. IL-13 down-regulates the hsp65-induced CTL generation and counteracts the positive effect of IL-18. The negative effect of IL-13 is observed in the early stages of the response, suggesting that this cytokine affects IFNgamma production by NK cells. mRNA coding for IFNgamma is induced by IL-18 and reduced in the presence of IL-13, when PBMC from N or PB patients are stimulated with hsp65. Neutralization of IL-13 in PBMC from multibacillary (MB) leprosy patients induces the production of IFNgamma protein by lymphocytes. A modulatory role on the generation of hsp65 induced CTL is demonstrated for IL-18 and IL-13 and this effect takes place through the production of IFNgamma.</p>  a0009-9104