03182nas a2200505   4500000000100000008004100001260001300042653001500055653001000070653000900080653002400089653002300113653003100136653001800167653001600185653003000201653002000231653001100251653001100262653002100273653001900294653001800313653001800331653001800349653002600367653002600393653000900419653001600428653002500444653002900469653003200498100001600530700002000546700001100566700001400577700001300591700001500604700001800619700001300637245021400650300001200864490000800876520177800884022001402662       1998                            d  c1998 Nov10aAdolescent10aAdult10aAged10aAntigens, Bacterial10aBacterial Proteins10aCD4-Positive T-Lymphocytes10aChaperonin 6010aChaperonins10aCytotoxicity, Immunologic10aDown-Regulation10aFemale10aHumans10aInterferon-gamma10aInterleukin-1010aInterleukin-210aInterleukin-410aInterleukin-610aKiller Cells, Natural10aLymphocyte Activation10aMale10aMiddle Aged10aMycobacterium leprae10aT-Lymphocytes, Cytotoxic10aTumor Necrosis Factor-alpha1 aSasiain M C1 aDe La Barrera S1 aFink S1 aFiniasz M1 aAleman M1 aFarina M H1 aPizzariello G1 aValdez R00aInterferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are necessary in the early stages of induction of CD4 and CD8 cytotoxic T cells by Mycobacterium leprae heat shock protein (hsp) 65 kD.  a196-2030 v1143 a<p>Cytotoxic T cells (CTL) may play an important role in host defence against mycobacterial infections. CD4 CTL are preferentially induced by mycobacteria, but both CD4 and CD8 CTL may be necessary components of a protective immune response. The 65-kD mycobacterium heat shock protein (hsp65) is a poor inducer of CTL in multibacillary leprosy (MB) patients. In this study we evaluate the possible role of cytokines in modulating the cytotoxic activity of CTL from leprosy patients and normal individuals (N) against autologous macrophages presenting Mycobacterium leprae hsp65. Our results show that hsp65-specific CTL were generated from both CD4 and CD8 lymphocytes. In N, individual cytokines as well as the combination of them were able to modify the hsp65-induced cytotoxic activity. The effect of cytokines on leprosy patients' lymphocytes was different in MB and paucibacillary (PB) patients. Thus, IL-6, IL-2, IFN-gamma or TNF-alpha did not modify the generation of hsp65-CTL from either MB (with or without an erythema nodosum episode (ENL)) or PB. In all the patients the simultaneous addition of two cytokines was required in order to increase CTL generation. In MB, IL-6 plus IFN-gamma or IL-2 increased both CD4 and CD8 CTL, while TNF-alpha plus IFN-gamma up-regulated only CD4 CTL. In PB, CD8 CTL were prominent with IL-6 plus IFN-gamma, while the increase was significant in CD4 CTL with IL-6 plus IL-2. Down-regulation of CTL was observed by addition of IL-4, IL-10, anti-IFN-gamma or anti-TNF-alpha in N controls. Our data demonstrate that IFN-gamma and TNF-alpha must be present for at least the first 60 h of the induction stage in order to generate full hsp65 CTL. Hence, IFN-gamma and TNF-alpha would be key factors in the generation of hsp65 CTL.</p>  a0009-9104