02467nas a2200373   4500000000100000008004100001260001600042653001400058653005300072653001100125653002100136653002100157653001900178653001800197653001200215653002500227653002500252653002600277653002500303653001800328653003200346100001600378700001500394700001500409700001400424700001400438700001200452700001500464245011900479300001200598490000800610520146100618022001402079       1993                            d  c1993 Jun 1510aCell Line10aGranulocyte-Macrophage Colony-Stimulating Factor10aHumans10aImmune Tolerance10aInterferon-gamma10aInterleukin-1010aInterleukin-410aleprosy10aLeprosy, lepromatous10aLeprosy, Tuberculoid10aLymphocyte Activation10aMycobacterium leprae10aT-Lymphocytes10aTumor Necrosis Factor-alpha1 aSieling P A1 aAbrams J S1 aYamamura M1 aSalgame P1 aBloom B R1 aRea T H1 aModlin R L00aImmunosuppressive roles for IL-10 and IL-4 in human infection. In vitro modulation of T cell responses in leprosy.  a5501-100 v1503 a<p>IL-10 and IL-4 have been shown to exert an inhibitory effect on cell-mediated immune responses. Our previous studies of leprosy demonstrated that IL-10 and IL-4 mRNA were preferentially expressed in lesions from lepromatous patients, those immunologically unresponsive individuals that manifest widespread infection. To define more precisely the regulatory roles of these two cytokines in the immune response to infection, we studied in vitro responses to Mycobacterium leprae. M. leprae triggered IL-10 release from PBMC of patients and healthy donors; the predominant source of the IL-10 was found to be monocytes/macrophages. Stimulation of PBMC in the presence of neutralizing anti-IL-10 mAb indicated that endogenous IL-10 production inhibits PBMC proliferation and release of TNF-alpha, GM-CSF, and IFN-gamma. Paradoxically, studies using neutralizing anti-IL-4 mAb indicated that endogenous IL-4 production enhances PBMC proliferative responses most strikingly in lepromatous patients. We found that rIL-4 expanded CD8+ T cells from lepromatous patients in vitro. CD8+ T cells from lepromatous patients have been shown to suppress CD4+ T cell responses, in part by the release of IL-4. Our study indicated that endogenous IL-4 production inhibited IL-10 secretion and, concomitantly, increased TNF-alpha and GM-CSF release. The present data suggest that, on balance, IL-4 and IL-10 contribute to immunosuppression in human infectious disease.</p>  a0022-1767