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)

Soluble serum interleukin 2 receptor levels in leprosy patients.

Soluble interleukin 2 receptors (IL-2R) in sera of leprosy patients from Chiang Mai, Thailand, were quantified with a solid phase enzyme immunoassay using two monoclonal antibodies to the IL-2R. The IL-2R levels of untreated lepromatous, borderline lepromatous or midborderline patients and treated lepromatous and borderline lepromatous or treated borderline tuberculoid and tuberculoid patients were comparable to those of the Thai household or nonhousehold contacts; and they were significantly higher than the levels of USA control subjects. In contrast, IL-2R of untreated tuberculoid or borderline tuberculoid patients were significantly reduced. Patients with ongoing reversal reaction had very high circulating IL-2R, the levels of which correlated with fever and extent of skin lesions. Although erythema nodosum leprosum patients also had elevated IL-2R levels, they were significantly below those of patients with reversal reaction. When treated with corticosteroid, precipitous reduction of IL-2R was noted in all patients with reversal reaction but not in patients with erythema nodosum leprosum.

Lymphocyte transformation in lepromatous leprosy: a study of the influence of disease activity and symptom duration.

The lymphocyte hyporesponsiveness to M. leprae of patients with active lepromatous leprosy has been well described. This immune defect is less well understood in terms of its time of origin, possible reversibility and specificity. To further examine the persistence and specificity of this abnormality, lymphocyte transformation tests of 93 leprosy patients to lepromin, BCG and PHA were studied. Among lepromatous patients, a decreased response to M. leprae was seen, whether the disease was active or inactive. Decreased responses to BCG were found in lepromatous patients with active disease, but not in those with inactive disease. The duration of patient symptoms was not associated with differences in LTT responses among the active lepromatous patients.

A study of the immunological effects of cimetidine in patients with lepromatous leprosy.

To test the capacity of cimetidine to enhance cellular immunity in patients with lepromatous leprosy (LL), cimetidine was given for one month to 29 inactive LL patients and 3 active LL patients. Immune function was monitored with skin tests (lepromin, PPD, candida, and trichopytin), lymphocyte transformation tests (phytohemagglutinin, BCG, and Dharmendra lepromin), and quantitation of peripheral blood lymphocyte subpopulations. A small but significant "booster" response to PPD was the only change observed in the study of patients with inactive disease, and leprosy-related reactions did not occur. In the few active LL patients studied, neither immune enhancement nor leprosy-related reactions were observed. The results of this investigation suggest that cimetidine can be used safely in patients with inactive lepromatous leprosy.

Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand.

A study of the frequency of HLA-DR2 and DQw1 was performed in leprosy patients and controls in northern Thailand. HLA-DR2 was found in 100% (17/17) of patients with sporadic tuberculoid leprosy and in over 90% (30/32) of all tuberculoid leprosy patients, as compared to 62% (20/32) of controls (p = .02). These strong associations had relative risks of 21.4 for sporadic and 7.4 for all tuberculoid leprosy, and etiologic fractions of 1.0 and 0.84, respectively. There was also a statistically significant and strong association between tuberculoid leprosy and DQw1. These data add to the growing body of evidence that products of HLA class II determinants or closely linked genes may play a role in determining the clinical manifestations of M. leprae infection.