02511nas a2200313   4500000000100000008004100001260001300042653002400055653004400079653001100123653001800134653001200152653002600164653002400190653002500214653001800239100001600257700001200273700001200285700001200297700001100309700001600320700001300336245004300349300001100392490001500403520176500418022001402183       1992                            d  c1992 Aug10aAntigens, Bacterial10aDose-Response Relationship, Immunologic10aHumans10aInterleukin-210aleprosy10aLymphocyte Activation10aMycobacterium bovis10aMycobacterium leprae10aT-Lymphocytes1 aMullins R J1 aRoche P1 aAdams E1 aJones P1 aChen S1 aTheuvenet W1 aBasten A00aLimiting dilution analysis in leprosy.  a277-900 v70 ( Pt 4)3 a<p>Peripheral blood mononuclear cells (PBM) obtained from leprosy patients and healthy controls were cultured with Mycobacterium leprae and the control antigens, BCG and SKSD. Parallel cultures were supplemented with additional interleukin-2 (IL-2). On the basis of the level of response to M. leprae, leprosy patients could be divided into low, intermediate and high responders. The addition of IL-2 resulted in enhanced proliferation to antigen only by cells from intermediate responders. This effect was neither antigen specific nor was it confined to cells from leprosy patients. When limiting dilution analyses were performed on cells from 26 patients across the leprosy spectrum, no M. leprae-reactive lymphocytes were detected in cells from subjects with lepromatous disease. The precursor frequency for cultures containing M. leprae plus IL-2 was no greater than that of cultures containing IL-2 alone, thereby excluding the possibility of clonal anergy reversible with IL-2. This was observed in both untreated patients and those on long-term treatment, which made sequestration of antigen-reactive cells within leprosy lesions an unlikely explanation. On the other hand, M. leprae-reactive lymphocytes were detected in patients with tuberculoid and borderline tuberculoid disease and in two subjects with borderline lepromatous leprosy in type I reversal reaction. IL-2 reactive cells were detected in all patients regardless of clinical classification. Three 'suppressor' curves were obtained but were not confined to cells from lepromatous patients. Taken together, these findings suggest that the non-responsiveness to M. leprae characteristic of the great majority of multibacillary patients is due to an absence of antigen-sensitive T cells.</p>  a0818-9641