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Biomedical subjects

R L Modlin

Publications and source records attributed to R L Modlin.

At least 145 records · Page 8Linked to original sources
PubMed1988

The immunology of tuberculous pleurisy.

Tuberculous pleurisy results when a subpleural nodule discharges mycobacterial antigens into the pleural space of a hypersensitive host. The clinical syndrome is a reflection of an in situ delayed-type hypersensitivity reaction in which plasma proteins are exuded into the pleural space and T-helper cells accumulate, proliferate, and produce, and release inflammatory mediators. The immune response initially contains the local infection, but in the absence of therapy, the host is at great risk of developing tuberculosis during the next 5 years. The focal accumulation of vigorously responsive T-helper cells and activated B cells in the pleural space may prove useful in identifying mycobacterial constituents which are immunogenic and possibly candidate vaccine antigens.

Animals↗
PubMed1987

Lepromin-induced suppressor cells in lepromatous leprosy.

The presence or absence of suppressor cells in leprosy patients was investigated by measuring peripheral blood lepromin-induced suppression of the Con A response. Significant suppressor activity was measured in 15 of 15 untreated or recently treated patients with lepromatous leprosy and 3 of 5 patients with borderline lepromatous leprosy. In addition, in patients with lepromatous leprosy, suppressor cell activity was found in 10 of 14 patients that had been under treatment for more than 1 year but in only 2 of 27 patients who had active or thalidomide controlled erythema nodosum leprosum. Suppression was observed in only 5 of 29 tuberculoid leprosy patients, 1 of 6 patient contacts, and 0 of 11 normal controls. The differences between the lepromatous or borderline lepromatous group as compared with the tuberculoid group were statistically significant (P less than 0.001). Our findings confirm the presence of lepromin-triggered suppressor cells in the peripheral blood of patients with lepromatous leprosy. These suppressor cells may contribute to the selective unresponsiveness of lepromatous patients to the antigens of Mycobacterium leprae.

Concanavalin A↗
PubMed1987

Leprosy: new insight into an ancient disease.

Patients with leprosy may be classified into two clinical and histopathologic categories. At one end of the spectrum, patients with tuberculoid leprosy have few skin lesions in which organisms can rarely be identified. At the other end of the spectrum, patients with lepromatous leprosy have numerous skin lesions containing myriad bacilli. Because immunologic resistance is associated with this spectrum, the study of leprosy provides a unique opportunity to gain insight into immunoregulatory mechanisms in man. In addition, serodiagnosis to identify early cases and prevention by vaccination are areas of active research. For patient care, a network of Regional Hansen's Disease Centers has been established under the sponsorship of the National Program for Hansen's Disease, Carville, LA. Because the patients are often poor, their receipt of care and medication without cost helps to ameliorate at least one of the burdens imposed by this potentially devastating illness. The program central office may be called at 800-642-2477.

Humans↗
PubMed1987

In situ identification of activated Ta1+ T lymphocytes in human leprosy skin lesions.

Using a monoclonal antibody, anti-Ta1, that identifies antigen-activated T lymphocytes in vitro, we sought to identify activated T lymphocytes in leprosy skin lesions. Greater numbers of Ta1 positive T lymphocytes were observed in tuberculoid leprosy, lepromin skin tests, and reversal reactions as compared with lepromatous leprosy or erythema nodosum leprosum (ENL) (p less than 0.001). With a double-staining technique, we found that the majority of these activated T lymphocytes were of the helper/inducer phenotype. No differences of Ta1 positive lymphocytes were observed in the peripheral blood. The defective cell-mediated immune response in lepromatous and ENL patients correlates with, and may be related to the failure of T-helper/inducer activation or proliferation in the presence of Mycobacterium leprae.

Antibodies, Monoclonal↗
PubMed1987

Immunohistological evidence of lymphokine production and lymphocyte activation antigens in tuberculin reactions.

Evidence of lymphokine elaboration and lymphocyte activation was sought in tuberculin skin test reactions at 24 and 48, or 48 and 96 h in patients with active, culture-proven, pulmonary tuberculosis. Through the use of frozen sections, immunoperoxidase techniques and monoclonal antibodies, anti-interleukin 2 positive cells were found to constitute 0.4% to 0.6% of the dermal infiltrate, and keratinocyte Ia expression at 96 h was consistent with a marker for interferon-gamma production. Cells bearing the interleukin 2 receptor more than doubled in prevalence from 24 to 48 or 96 h but cells staining with Ta1, an antibody identifying activated lymphocytes, were 10% of the cells of the infiltrate at all three times. One-half of the cells of the infiltrate were OKM1-positive, presumably macrophages, perhaps reflecting the presence of active tuberculosis.

Antigens, Surface↗
PubMed1986

Effect of cyclosporine A in erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is a reactional state of lepromatous leprosy in which the loss of suppressor cell function, decrease in suppressor cell numbers, and increase of interleukin 2 production are observed. We reasoned that cyclosporine A (CsA), by opposing these immune responses, could suppress the ENL reaction and restore patients to the quiescent lepromatous state. We tested this hypothesis in vitro by measuring the effect of CsA on M. leprae-triggered suppressor cells. In 24 of 25 patients with ENL, suppressor cell activity was restored by CsA. The target of CsA appeared to be macrophages. These findings are significant in that they provide the first evidence for the potential efficacy of CsA in the treatment of ENL. Preliminary clinical trials indicate a beneficial therapeutic effect associated with increased T suppressor cells in lesions.

Cyclosporins↗
PubMed1986

Suppressor T lymphocytes from lepromatous leprosy skin lesions.

The immune response in leprosy forms a spectrum with lepromatous leprosy patients exhibiting specific unresponsiveness to antigens of Mycobacterium leprae. This unresponsiveness is thought to be related to the prevalence of T8-positive lymphocyte in these lepromatous lesions. To analyze the immunoregulatory function of these T8 cells, we developed simple procedures to extract lymphocytes from skin biopsy specimens of patients with leprosy. These lymphocytes were sorted for T8 and T4 positive cells, and cell lines were established by expansion with interleukin 2 (IL 2) and irradiated feeder cells. All T8 positive lines tested were positive for IL 2 receptors and HLA-DR determinants. These lines were additionally assayed for lepromin-induced suppression of the normal peripheral blood lymphocyte Con A proliferative response. Thirteen of 32 lines from six lepromatous patients showed significant suppressor activity, whereas nine lines from six tuberculoid patients and one line from normal peripheral blood failed to show suppression (p less than 0.001). Taken together, the finding of M. leprae-triggered suppressor cells within lepromatous skin lesions may in part explain the M. leprae unresponsiveness of lepromatous leprosy patients.

Antigens↗
PubMed1986

In situ and in vitro characterization of the cellular immune response in erythema nodosum leprosum.

We sought to evaluate cell-mediated immune responses in erythema nodosum leprosum (ENL), a reactional state occurring in lepromatous leprosy. Skin biopsies from patients with leprosy were studied with monoclonal antibodies against T lymphocyte antigenic determinants, interleukin 2 (IL 2), and IL 2 receptors (Tac) by using immunoperoxidase staining of frozen sections. Peripheral blood lymphocytes from 18 ENL patients were tested in vitro for lepromin-induced suppression of Con A stimulation. Serial studies of seven lepromatous patients who developed ENL during the course of the study showed increases in both the Leu-3a:Leu-2a ratio and the number of IL 2-positive cells. IL 2-positive cells comprised 0.3% of the cells in all of the ENL lesions studied as compared with the 0.03% found in nonreactional lepromatous lesions (P less than 0.001). Lepromin-induced suppression of the Con A response, present in nonreactional lepromatous patients, significantly decreased in patients developing the ENL reaction, but returned after recovery from ENL. These changes in tissues and peripheral blood suggest that the pathogenesis of ENL is related to cell-mediated immune processes. Despite these immunologic changes, however, ENL patients do not recover antigen-specific skin tests or eliminate Mycobacterium leprae.

Antibodies, Monoclonal↗
PubMed1986

In situ detection of amastigotes in American cutaneous leishmaniasis, using monoclonal antibodies.

Using an immunoperoxidase technique we have applied monoclonal antibodies against American Leishmania for the detection of amastigotes in biopsies from cutaneous leishmaniasis patients. The immunocytochemical procedure was notably superior to conventional histological staining in terms of the visualization and definition of the amastigotes. This technique could eventually prove to be of value in epidemiological studies, and possibly have prognostic importance, by allowing the in situ characterization of the species of infecting organism.

Antibodies, Monoclonal↗
PubMed1986

Human monoclonal antibodies that distinguish cutaneous malignant melanomas from benign nevi in fixed tissue sections.

Human monoclonal antibodies were generated by fusing a nonsecretory variant of murine myeloma cells with lymphocytes obtained from the lymph nodes of patients with metastatic cutaneous malignant melanoma. Two human IgG monoclonal antibodies, designated 2-139-1 and 6-26-3, were extensively studied for their patterns of binding to cells in 64 specimens of formalin-fixed, paraffin-embedded tissue sections. These comprised: 23 cutaneous and 2 ocular melanomas; 4 specimens of lentigo maligna; 27 benign nevi; 2 basal and 2 squamous cell neoplasms of the skin; and 4 specimens of normal skin. A direct avidin-biotin-immunoperoxidase staining method was used. Under these conditions, the antibodies reacted with variable intensity to all 18 primary cutaneous malignant melanomas, 5 metastatic cutaneous melanomas, and both ocular melanomas. Antibody 2-139-1 reacted with 1 of 4 specimens and 6-26-3 with 3 of 4 specimens of lentigo maligna. Two of 5 dysplastic nevi reacted with both antibodies, each with a smaller proportion of cells than with melanomas. There was no reactivity with the 22 other nevi representing a spectrum of histologic types or with normal melanocytes. Basal cell and squamous cell carcinomas of the skin also were not stained. These human monoclonal antibodies appear to be useful in distinguishing malignant melanomas from benign nevi, with the exception of dysplastic nevi, and from basal and squamous cancers of the skin in routinely prepared tissue sections. They may also help to identify the cytoplasmic antigens that are immunogenic in humans.

Antibodies, Monoclonal↗
PubMed1986

Epidermal keratinocyte Ia expression, Langerhans cell hyperplasia and lymphocytic infiltration in skin lesions of leprosy.

Epidermal changes, Ia expression on keratinocytes, Langerhans cell hyperplasia and lymphocyte infiltration were sought in skin lesions of leprosy: 15 borderline tuberculoid (BT), six borderline lepromatous (BL), 17 lepromatous (LL), 13 erythema nodosum leprosum (ENL), six Lucio reactions and nine reversal reactions. All three changes were well developed in BT and reversal reactions. ENL showed well developed keratinocyte Ia and Langerhans cell hyperplasia, but little lymphocytic infiltration. LL and Lucio tissues had some Langerhans cell hyperplasia but little or no keratinocyte Ia or lymphocytic infiltration. BL tissues were so diverse as to suggest two distinct subgroups. These findings are consistent with the hypothesis that keratinocyte Ia expression is an immunohistological sign of a cell-mediated immune (CMI) response. However, the Ia keratinocyte expression found in BL and ENL tissues appears contrary to the undifferentiated macrophages and numerous bacilli found in the lesions. Thus, if a sign of CMI, keratinocyte Ia expression is not a measure of the effectiveness of the response.

Cell Movement↗
PubMed1986

In situ characterization of T lymphocyte subpopulations in leprosy in the mangabey monkey.

Leprosy in the mangabey monkey is an experimental model which is similar both clinically and histologically to human lepromatous leprosy. The immunopathology of these diseases was compared using monoclonal antibodies against T lymphocyte subpopulations in frozen tissue sections with an immunoperoxidase technique. In both mangabey and human lepromatous granulomas OKT4 (or Leu 3a) and Leu 2a cells were scattered among macrophages with greater numbers of Leu 2a as compared with OKT4 (or Leu 3a) cells. The results suggest that from an immunopathological standpoint experimental leprosy in mangabeys will provide a suitable model for the investigation of the pathogenesis of human lepromatous leprosy and for the evaluation of new antileprosy vaccines.

Animals↗
PubMed1985

In situ localization of T lymphocytes in disseminated coccidioidomycosis.

Immunohistochemical techniques using monoclonal antibodies to T lymphocyte subpopulations were used to characterize further the granulomas of disseminated coccidioidomycosis. Skin biopsy specimens from patients with disseminated coccidioidomycosis were studied and compared with tissues from experimentally infected mice. In human skin biopsy specimens and infected mouse tissues, discrete granulomata were seen in which T lymphocytes formed a peripheral mantle surrounding central aggregates of macrophages. This unusual pattern of granuloma formation may represent an ineffective host response because these individuals are unable to clear their infection. Because of the close similarity of immunopathology in both human and mouse infections, the mouse model should serve as a useful tool in elucidating the factors contributing to ineffective host responses in systemic fungal infections.

Adolescent↗
PubMed1985

Distribution of cells bearing the Tac antigen during ontogeny of human lymphoid tissue.

The monoclonal antibody anti-Tac, which binds to the interleukin 2 (IL 2) receptor, was used to identify this antigen in human fetal and adult lymphoid tissue. Liver, spleen, thymus, lymph node, and peripheral blood were examined for Tac-positive cells with the use of frozen sections or cytocentrifuge preparations. The results show that cells in the fetal and neonatal thymus express the Tac antigen; these cells are predominantly located in the medulla. The liver and spleen of both fetus and adult exhibit very few Tac-positive cells. Double staining demonstrates that cells bearing the Tac-antigen stain with Leu-4, an anti-T cell antibody. In adult lymph node tissue, the Tac-bearing cells are predominantly distributed in the interfollicular area, with positive cells also present in the germinal center and mantle zone. The Tac antigen is present on both T and B cells. Few Tac-positive cells are present in the circulating peripheral blood.

Adult↗
PubMed1985

Tissue and blood T-lymphocyte subpopulations in erythema nodosum leprosum.

To study T lymphocytes in erythema nodosum leprosum (ENL), monoclonal antibodies were used to identify T-lymphocyte subpopulations in the blood and skin lesions of patients with ENL and patients with nonreactional lepromatous leprosy. The blood of nonreactional lepromatous patients had a lymphopenia and a proportionate reduction in pan T cells, helper-inducer, and suppressor-cytotoxic subsets, but a normal helper-suppressor ratio, as compared with controls. Patients with ENL did not differ significantly from the controls. In skin lesions, an admixture of helper and suppressor phenotypes among foamy histiocytes was found. The ENL tissue had more numerous cells of the helper-inducer phenotype and fewer of the suppressor-cytotoxic phenotype, as compared with nonreaction lepromatous tissues. In 22 patients with simultaneous examination of tissue and blood T-cell subsets, there was no correlation between tissue and blood helper-suppressor ratios, indicating that some sort of selection process brings lymphocytes into tissues from peripheral blood.

Cell Count↗
PubMed1985

In situ characterization of the cellular immune response in American cutaneous leishmaniasis.

American cutaneous leishmaniasis is a spectrum of granulomatous disease caused by related species of an intracellular parasite. The host response in localized cutaneous leishmaniasis (LCL) is effective in that few organisms can be found in tissue lesions. In contrast, diffuse cutaneous leishmaniasis (DCL) patients mount a poor response with numerous parasites present in multiple skin lesions. Immunopathological correlates were sought in LCL and DCL with immunoperoxidase techniques using monoclonal antibodies directed against T lymphocyte subpopulations and interleukin-2 in tissue lesions. Both LCL and DCL granulomas showed a mixture of T lymphocyte subpopulations with the ratio of helper:suppressor phenotypes less than one. This ratio and localization of cells is more similar to the ineffective lepromatous leprosy granuloma than the effective tuberculoid leprosy granuloma. In contrast, interleukin-2 was identified in equivalent numbers of cells in LCL and tuberculoid leprosy, an order of magnitude greater than DCL and lepromatous leprosy lesions. Cells expressing Tac, the receptor for interleukin-2, were present in approximately equal numbers in all disorders. The immunological effectiveness of granulomas appear to related less to the numbers and location of T cell phenotypes than to the functional aspects of these cells, particularly the ability to generate lymphokines.

Granuloma↗
PubMed1985

An in situ immunohistological study of Mitsuda reactions.

In an attempt to further define their immunopathogenesis, the cellular infiltrates of Mitsuda reactions were studied in situ using immunoperoxidase techniques and monoclonal antibodies. Lepromin A-elicited Mitsuda reactions from six patients with borderline tuberculoid leprosy (TT/BT or BT) and three healthy kindred and contacts of lepromatous patients were examined. In the dermis, cells bearing the Leu4 phenotype comprised a mean of 61% of the infiltrate; the Leu3a, 47%; the Leu2a, 17%; anti-IL-2, 0.2%; anti-Tac, 1.5%; and cells bearing the Ia phenotype were virtually universal; OKT6 positive cells were present. The Leu2 phenotype was sequestered to the periphery of epithelioid tubercules. In the epidermis, there were mild, focal lymphocytic infiltrates, hyperplasia of epidermal Langerhans' cells, and well-developed expression of Ia upon nucleated keratinocytes. These findings, when compared with those of a better-defined reaction, tuberculin, are further evidence that the Mitsuda response may be a delayed-type hypersensitivity phenomenon.

Humans↗