T-lymphocyte clones from leprosy skin lesions.
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Clone Cells↗
Biomedical subjects
R L Modlin
Publications and source records attributed to R L Modlin.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Demonstration in situ of subsets of T-lymphocytes in sarcoidosis.
Five biopsy specimens of skin, four of lung, and one of a lymph node were taken from nine patients with sarcoidosis. Monoclonal antibodies were applied to frozen sections of the specimens by an immunoperoxidase technique to test for the presence and distribution of subsets of T-lymphocytes. T-cells expressing the suppressor/cytotoxic phenotype were found predominantly in lymphocytic mantles surrounding sarcoidal granulomas, whereas cells displaying the helper/inducer phenotype were distributed diffusely throughout granulomas. The ratio of helper to suppressor phenotypes in cutaneous sarcoidosis was 5.1 +/- 1.8. The microanatomic location of subpopulations of T-lymphocytes may be important in the pathogenesis of the granulomatous response of sarcoidosis.
Antibodies, Monoclonal↗
Comparison of S-100 and OKT6 antisera in human skin.
The monoclonal antibody OKT6 and antisera against S-100 protein have both been advocated as immunologic markers of Langerhans cells in the skin. S-100 antiserum has an advantage in its ability to stain Langerhans cells in paraffin tissues. In order to evaluate whether these antibodies stain equivalent numbers of Langerhans cells in skin, we compared the staining patterns of S-100 antiserum and OKT6 antibody on biopsy specimens from 40 patients with leprosy using immunoperoxidase techniques. Utilizing OKT6 antibody, greater numbers of positive Langerhans cells were found in the epidermis in tuberculoid leprosy, reversal reaction, and erythema nodosum leprosum than in lepromatous leprosy. However, these differences were not observed with the S-100 antiserum and, overall, fewer cells were found as compared with the OKT6 antibody. In the dermis both antibodies stained "dendritic cells" that were found encircling granulomas in tuberculoid leprosy and reversal reaction. Staining in lepromatous leprosy granulomas, in contrast to the epidermal staining pattern, revealed rare OKT6-positive cells, while S-100 cells were numerous and were more diffusely distributed throughout the granuloma. Our results indicate that antiserum to S-100 protein and OKT6 antibody stain morphologically similar cells (dendritic cells), but do not provide comparable results concerning distribution and frequency of these cells.
Antibodies, Monoclonal↗
Immunopathologic demonstration of T lymphocyte subpopulations and interleukin 2 in granuloma annulare.
Immunopathologic aspects of granuloma annulare were studied in frozen sections of nine skin biopsy specimens with monoclonal antibodies directed against T lymphocytes, Langerhans' cells, interleukin 2, and interleukin 2 receptors in conjunction with immunoperoxidase techniques. The predominant lymphocyte was an activated T lymphocyte (Leu 1+, HLA-DR+) with an excess of helper/inducer phenotype (Leu 3a+) as compared with suppressor/cytotoxic phenotype (Leu 2a+). Langerhans' cells were increased in the epidermis and numerous OKT6+ cells were observed in the perivascular and granulomatous infiltrate. Both interleukin 2-positive cells and interleukin 2 receptor-positive cells were identified in the dermal lesions according to observed reactivity with the corresponding monoclonal antibodies. These findings suggest that a cell-mediated immune response producing cytokines may be important in the pathogenesis of granuloma annulare. Comparison of these results with skin specimens from patients with sarcoidosis and from a patient with granuloma annulare having some of the histologic features of sarcoidosis, suggests that the cutaneous infiltrate in granuloma annulare represents a response distinct from that of sarcoidosis.
Antibodies, Monoclonal↗
Kaposi's sarcoma and autoimmune thrombocytopenia.
Outbreaks of Kaposi's sarcoma, opportunistic infections, and autoimmune thrombocytopenia among homosexual men have recently been described. We report here a case with the combination of Kaposi's sarcoma and autoimmune thrombocytopenia. Our patient presented with Kaposi's sarcoma limited to the integument and autoimmune thrombocytopenia diagnosed by elevated platelet bound IgG. Characteristics of immunosuppression included lymphocytopenia and a reversed blood helper:suppressor T lymphocyte ratio. Immunohistochemical evaluation of skin biopsy specimens revealed tumor cells to contain Factor VIII-related antigen (a vascular endothelial cell marker). In addition some tumor cells stained positively with a monoclonal antibody directed against a cytomegalovirus antigen.
Adult↗
Identification of cells lining pseudovascular spaces of benign pigmented nevi.
So-called pseudovascular spaces, said to occur in 10% of benign pigmented nevi, are presumed to be shrinkage artifacts of tissue processing. In an attempt to characterize the cells lining these spaces, three benign pigmented nevi were studied with immunoperoxidase techniques. It was found that they stained positively with an anti-melanoma antibody, P97a (gamma-2a), but negatively with an antibody against an antigen-related factor VIII, which is a marker for vascular endothelium. We conclude that these spaces are lined by melanocytes of nevi and that the spaces are not truly vascular. In one specimen, the spaces were filled with erythrocytes, which suggest that the spaces were present before fixation. It has been suggested, though, that altered collagen and elastic tissue and the nevi themselves may diminish the resistance of the dermis to the mechanical stress of the biopsy procedure, which results in the formation of these spaces.
Antibodies, Neoplasm↗
In situ identification of cells in human leprosy granulomas with monoclonal antibodies to interleukin 2 and its receptor.
Leprosy is a chronic granulomatous disease with an immunologic spectrum in which lepromatous leprosy patients have defective cell-mediated immune responses, in comparison to tuberculoid leprosy patients. Immunoregulatory aspects of this spectrum were investigated by using monoclonal antibodies to interleukin 2 (IL 2), IL 2 receptors (Tac), and T lymphocyte subpopulations with immunoperoxidase techniques on frozen sections of skin biopsy specimens from 10 tuberculoid and 10 lepromatous patients. A comparison of IL 2+ cells revealed markedly fewer IL 2+ cells in lepromatous specimens (lep. 0.028% +/- 0.02 vs tub. 0.46% +/- 0.28, p less than 0.001). These IL 2+ cells were large, exhibited cytoplasmic staining, and on double immunostaining were Leu-4+, Leu-3a+, Leu-2a-, Tac-, and OKT6-, consistent with the fact they are IL 2 producers. Equivalent numbers of Tac+ cells were observed in both lepromatous and tuberculoid granulomas (lep. 1.5% +/- 0.5 vs tub. 2.1% +/- 0.7, p, NS), suggesting that the responder cells are present in both conditions. The tuberculoid granuloma was highly organized, composed of a central core of mature macrophages, Leu-3a+ and Tac+ cells with a surrounding mantle of Leu-2a+, Leu-3a+, IL 2+, Tac+, and OKT6+ cells. In lepromatous granulomas, Leu-2a+, Leu-3a+, Tac+, and rare IL 2+ cells were randomly admixed with bacilli-laden macrophages. The defective cell-mediated immune responses in lepromatous leprosy appears to be associated with diminished IL 2 production and disorganization of the granuloma.
Antibodies, Monoclonal↗
Peripheral blood T lymphocyte subsets in leprosy.
Peripheral blood T lymphocyte subsets were measured by flow cytometry in 122 patients with leprosy, in 23 normal controls, and in 27 patients with systemic lupus erythematosus (SLE). Active lepromatous patients not in reaction showed a significant lymphopenia and a significant proportionate reduction in the number of OKT3-positive (pan T), OKT4-positive (helper/inducer), and OKT8-positive (suppressor/cytotoxic) cells, but no alteration in distribution as judged by percentage and no abnormality in the helper: suppressor ratio. Borderline lepromatous subjects not in reaction had a significant selective deficiency in the number of cells of the OKT4-positive subset, with a significant but secondary lymphopenia and OKT3-positive cytopenia, a pattern similar to that found in SLE patients. Patients undergoing reversal reactions had a selective deficiency in the OKT4-positive subset in both absolute numbers and as a percentage of total lymphocytes, and a secondary deficiency in the percentage of OKT3-positive cells. No abnormalities were demonstrated in patients with active erythema nodosum leprosum, lepromatous patients with long-term treatment, and untreated or treated borderline tuberculoid patients.
Humans↗
Granuloma annulare. Identification of cells in the cutaneous infiltrate by immunoperoxidase techniques.
To characterize the immunopathologic process of granuloma annulare, frozen sections of eight specimens were evaluated with monoclonal antibodies directed against T lymphocytes and the monocyte-macrophage series, in conjunction with immunoperoxidase techniques and with histochemical staining. The predominant lymphocyte was an activated T lymphocyte (Leu 1+, HLA-Dr+) with an excess of helper-inducer phenotype (Leu 3a+), as compared with suppressor-cytotoxic phenotype (Leu 2a+). OKT-6+ Langerhans' cells were observed in the epidermis, and numerous OKT-6+ cells were observed in the perivascular and granulomatous infiltrate. The use of four monoclonal antibodies, having specificity against peripheral blood monocyte antigens, revealed three different staining patterns in the granulomas. Finally, mast cells were present in perivascular and granulomatous infiltrates. Our results demonstrate that the cutaneous infiltrate of granuloma annulare contains all of the principal cell types that characterize cell-mediated immune responses.
Antibodies, Monoclonal↗
Altered distribution of B and T lymphocytes in lymph-nodes from homosexual men with Kaposi's sarcoma.
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B-Lymphocytes↗
T-lymphocyte subsets in lymph nodes from homosexual men.
To evaluate further the immunodeficiency of homosexual men, blood and lymph node specimens were obtained from five homosexual men with lymphadenopathy and from seven homosexual men with Kaposi's sarcoma. Monoclonal antibodies were used to identify T-lymphocyte subsets in blood by cytofluorometry and in frozen sections of nodes by immunoperoxidase techniques. The homosexuals with Kaposi's sarcoma had a T-helper/suppressor ratio in blood of 0.7; the homosexuals with lymphadenopathy had a ratio of 0.6, compared with controls of 2.1. Control lymphoid tissue had a ratio of 3.0 in the interfollicular areas compared with the reactive lymph nodes in the homosexuals with lymphadenopathy, which was 0.7, and nodes from patients with Kaposi's sarcoma, 0.9. The nodes from homosexual men had evident numerous suppressor cells in the follicular center and mantle regions, locations in normal lymphoid tissue where suppressor cells were uncommon.
Flow Cytometry↗