Immunologic defects in leprosy patients. I. Evidence of immune aberration of suppressor-T lymphocytes in lepromatous leprosy.

Immunoregulation in various types of leprosy patients was evaluated in vitro using peripheral blood mononuclear leukocytes (PBML) stimulated with phytohemagglutinin-P (PHA-P) or concanavalin A (ConA) for a cell-mediated immune (CMI) assay or pokeweed mitogen (PWM) for a humoral-mediated immune (HMI) assay. The immune responses were evaluated by a lymphocyte transformation test (LTT) and lymphocyte-mediated cytotoxicity (LMC) for the immunoregulation of CMI, and a reverse hemolytic plaque assay for measuring the plaque-forming cells (PFC) and a sandwich ELISA for measuring IgG concentrations for the immunoregulation of HMI. In LTT with PHA-P or ConA, the mean of the normal controls was not significantly different from the means of the untreated LL, BL, BB, BT, and TT leprosy patients. However, a wide variation of LTT results from BT to LL patients was noted: the LTT results of TT patients and normal controls were less variable. A similar pattern of immune responses was noted when studied by LMC in untreated LL, BL, BB, BT, and TT leprosy patients and normal controls. When the untreated patients and normal controls were studied for PFC, using PBML stimulated with PWM, a very similar pattern of PFC was obtained with the different types of leprosy patients. The immunoregulatory role of lymphocytes in leprosy patients was further evaluated by cell mixing cultures. ConA-stimulated PBML from lepromatous leprosy patients were mixed with normal PBML and then stimulated with PHA-P.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic defects in leprosy patients. II. Interleukin 1, interleukin 2, and interferon production in leprosy patients.

The capabilities of monocytes and lymphocytes in peripheral blood mononuclear leukocytes (PBML) to produce interleukin-1 (IL-1), IL-2, and interferon (IFN), respectively, were evaluated in various types and treatments of leprosy patients. IL-1 production in response to lipopolysaccharide was significantly lower in LL, BL, BB, and BT patients than in normal controls. However, there were no differences in IL-1 levels between TT patients and normal controls. The percentages of nonspecific-esterase-positive cells adhering to the plastic surfaces were not different in LL, BB and TT patients when compared to normal controls. However, they were significantly higher in BT and BL patients than in normal controls. When PBML from leprosy patients were stimulated with concanavalin-A (ConA) for IL-2 production, there were no differences in the IL-2 levels in treated BL/LL, untreated BL/LL, treated BT/TT, and untreated BT/TT patients compared to normal controls. Similar results were obtained when PBML were stimulated with phytohemagglutinin-P (PHA-P). However, when purified protein derivative (PPD) was used as the stimulating agent, there were significantly lower IL-2 levels in treated BL/LL, untreated BL/LL, treated BT/TT, and untreated BT/TT patients when compared to normal controls. There were also lower IL-2 levels in untreated BL/LL and BT/TT patients compared to treated BL/LL and BT/TT patients, respectively. PBML were stimulated with PHA-P or ConA for IFN production.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro suppression of interleukin 2 production by Mycobacterium leprae antigen.

The suppressive activity of three different lots and sources of Mycobacterium leprae (M. leprae) was studied by measuring the inhibitory effect on interleukin 2 (IL-2) production in normal subjects. All three M. leprae preparations had suppressive activity on IL-2 production when peripheral blood mononuclear leucocytes (PBML) were stimulated with the mitogens PHA-P or Con A in a dose response. M. leprae also had suppressive activity on IL-2 production when PBML were stimulated with the specific antigen, PPD. The inhibitory activity of M. leprae on IL-2 was not due to the direct interaction of M. leprae and IL-2 because direct mixing of IL-2 with different concentrations of M. leprae did not alter the activity of IL-2. Incorporation of M. leprae for 0, 6 and 12 h in PHA-P and PBML cultures had no inhibitory effect on IL-2 production; however, after 14, 16 and 18 h of M. leprae incorporation, significant inhibitory effects were noted on IL-2 production. The suppressive mechanism of M. leprae was studied by incorporating M. leprae into PBML or adherent cells. The suppressive activity could be detected in both M. leprae-stimulated PBML and M. leprae-stimulated monocyte supernatant fluids. The suppressive mechanism of M. leprae was further evaluated by incorporating 1 and 2 micrograms/ml of indomethacin in PBML containing PHA-P and M. leprae. The suppressive activity of M. leprae was significantly diminished by indomethacin, suggesting that the inhibitory effect of M. leprae may result from the induction of PBML and adherent cells to produce the immunosuppressive activity of prostaglandin(s).