Tissue and blood T-lymphocyte subpopulations in erythema nodosum leprosum

Modlin, Robert L.

doi:10.1001/archderm.121.2.216

Cited by 16 publications

(9 citation statements)

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“…In contrast, ENL reactions may be visualized as a transient diminution of Ts activity, leading to partial augmentation of Th activity. We have reported a transient diminution of Ts activity in vitro during ENL episodes (24) . The diminution of Ts regulation could account for the augmentation of both cell-mediated immunity and antibody formation characteristic of ENL reactions.…”

Section: Discussionmentioning

confidence: 81%

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Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.

Cooper

Mueller

Sinchaisri

et al. 1989

The Journal of Experimental Medicine

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Leprosy provides a useful model for understanding immunoregulatory mechanisms in man. The disease forms a spectrum in which the immunologic response of the patient correlates with the clinical and histopathologic classification (1-3). At one end of the spectrum, patients with tuberculoid leprosy have one or several skin lesions in which bacilli can rarely be identified . CD4+ T lymphocytes predominate in these lesions (4-7) and respond to Mycobacterium leßrae in vitro (8). At the other end of the spectrum, patients with lepromatous leprosy have diffuse infiltration of skin and nerves with bacilli-laden macrophages. CD8+ cells predominate in lepromatous lesions and function as antigen-specific Ts cells in vitro (9, 10). The CD4+ lymphocytes derived from these lesions are unresponsive to M. leßrae . Imposed upon this spectrum are the so-called "reactional states" of reversal reaction and erythema nodosum leprosum (ENL)' that are of immunologic interest in understanding mechanisms of immunoregulation in man.The reversal reaction syndrome is associated with a marked rise in lymphocyte transformation to M. leßrae antigens in vitro, and is therefore thought to be a delayedtype hypersensitivity (DTH) reaction against M. leßrae antigens (11)(12)(13)(14)(15). Clinically, the condition is often associated with reduction or elimination of bacilli in lesions and sometimes followed by upgrading of the clinical and histological classification toward the tuberculoid pole. The pathogenesis of ENL reactions is somewhat controversial, thought to be due to immune complex deposition in the lesions (16-18) and/or increases in cell-mediated immunity (19,20).

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Section: Discussionmentioning

confidence: 81%

“…Immunohistologic study of skin lesions has thus far not distinguished between the immune processes underlying the pathogenesis of reversal reaction and ENL (21)(22)(23)(24)(25) . The inflammatory infiltrates in both reactional states are characterized by a predominance of CD4' lymphocytes .…”

mentioning

confidence: 99%

Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.

Cooper

Mueller

Sinchaisri

et al. 1989

The Journal of Experimental Medicine

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“…Conversely, helper T cells were the predominant population in the lesions. The prevalence of helper T cells at sites of disease introduces the concept of lymphocyte recirculation and stresses the point that the lesional infiltrate may not always reflect the peripheral blood cell subsets [7].…”

Section: Resultsmentioning

confidence: 99%

In situlocalization of T lymphocyte subsets in human paracoccidioidomycosis

Moscardi-Bacchi¹,

Soares

Mendes³

et al. 1989

Med Mycol

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lmmunohistochemical techniques using monoclonal antibodies to T lymphocyte subsets were used to characterize granulomas caused by Paracoccidioides brasiliensis. Punch biopsies of skin or mucosa from eight patients and of lymph nodes from two patients with disseminated paracoccidioidomycosis were studied. The T lymphocytes were distributed either in a localized pattern related to epithelioid granulomas or in a diffuse arrangement, predominantly around the vessels. In the granulomas, T cells formed a peripheral mantle surrounding central aggregates of macrophages. The majority of lymphocytes were T-helper cells with few suppressor cells. In contrast, patients presented with a decreased number of peripheral Thelper lymphocytes and a corresponding decrease in helper-suppressor cell ratios. There was no clear-cut relationship between tissue helper-suppressor cell ratios and the level of cellular immunodepression of the patients. The lowest P. brasiliensis antibody titers were detected in patients with the highest tissue helper-suppressor cell ratios. The distribution pattern of T lymphocytes in P. brasiliensis granulomas, with a predominance of helper phenotype, suggests that these cells are actively involved in the disease process.Paracoccidioidomycosis is a systemic disease caused by Paracoccidioides brasiliensis and is characterized mainly by involvement of the skin, mucosa, lungs, lymph nodes and adrenal glands. The histopathologic findings consist of epithelioid granulomatous inflammation with variable numbers of lymphomononuclear and polymorphonuclear cells.It has previously been shown that T lymphocytes from patients with paracoccidioidomycosis have a decreased reactivity to P. brasiliensis antigens, unrelated common antigens and mitogens, by several tests in vivo and in vitro [13]. The cell-mediated immunosuppression has been explained by a variety of potential mechanisms including host-produced serum-factors, immune complexes and suppressor cell populations [1,12,13].

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“…There is some evidence that changes in cell-mediated immune responses could facilitate antibody production in this reactional state. For example, there is a decrease in suppressor T-cell activity (20) and an influx of CD4+ memory T cells into ENL lesions (8,19).…”

Section: Discussionmentioning

confidence: 99%

Expression of adhesion molecules in leprosy lesions

et al. 1991

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Leprosy presents as a clinical spectrum that is precisely paralleled by a spectrum of immunological reactivity. The disease provides a useful and accessible model, in this case in the skin, in which to study the dynamics of cellular immune responses to an infectious pathogen, including the role of adhesion molecules in those responses. In lesions characterized by strong delayed-type hypersensitivity against Mycobacterium leprae (tuberculoid, reversal reaction, and Mitsuda reaction), the overlying epidermis exhibited pronounced keratinocyte intracellular adhesion molecule 1 (ICAM-1) expression and contained lymphocytes expressing the ICAM-1 ligand, LFA-1. Conversely, in lesions in which delayed-type hypersensitivity was lacking (lepromatous), keratinocyte ICAM-1 expression was low and LFA-1+ lymphocytes were rare. Expression of these adhesion molecules on the cells within the dermal granulomas was equivalent throughout the spectrum of leprosy. The percentage of lymphocytes in these granulomas containing mRNA coding for gamma interferon and tumor necrosis factor alpha, synergistic regulators of ICAM-1 expression, paralleled epidermal ICAM-1 expression. In lesions of erythema nodosum leprosum, a reactional state of lepromatous leprosy thought to be due to immune complex deposition, keratinocyte ICAM-1 expression and gamma interferon mRNA+ cells were both prominent. Antibodies to LFA-1 and ICAM-1 blocked the response of both ato and -y6 T-cell clones in vitro to mycobacteria. Overall, the expression of adhesion molecules by immunocompetent epidermal cells, as well as the cytokines which regulate such expression, correlates with the outcome of the host response to infection.

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Tissue and blood T-lymphocyte subpopulations in erythema nodosum leprosum

Cited by 16 publications

References 0 publications

Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.

Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.

In situlocalization of T lymphocyte subsets in human paracoccidioidomycosis

Expression of adhesion molecules in leprosy lesions

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