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J Convit

Publications and source records attributed to J Convit.

At least 37 records · Page 2Linked to original sources
PubMed1988

Learning from lesions: patterns of tissue inflammation in leprosy.

The clinical forms of leprosy constitute a spectrum that correlates closely with the degree of cell-mediated immunity. Patients with tuberculoid leprosy develop strong cell-mediated responses and have only a few, localized lesions, whereas patients with multibacillary lepromatous leprosy are specifically unresponsive to antigens of Myobacterium leprae. T cells of the CD4+ subset predominate in tuberculoid lesions, whereas CD8+ cells predominate in lepromatous lesions. Monoclonal antibodies that distinguish subpopulations of CD4+ and CD8+ cells were used to analyze the distribution of T cells infiltrating lesions across the disease spectrum. In lepromatous lesions, T cells of T-suppressor phenotype (9.3-) were the predominant CD8+ cells and suppressor/inducer cells (2H4+, Leu-8+) represented half of the CD4+ subset. In tuberculoid lesions, helper T cells (CD4+4B4+) outnumbered suppressor/inducer T cells by 14:1, compared with a ratio of 1.2:1 in peripheral blood. Analysis of the precursor frequency of antigen-reactive T cells permitted us to estimate that there was a 100-fold enrichment of T cells able to proliferate in response to M. leprae antigens in tuberculoid lesions (2/100), when compared with blood from the same patients. The methods used here to characterize the T-lymphocyte subsets and frequency of antigen-reactive T cells in leprosy may be useful in analyzing immunological reactions occurring in lesions of other inflammatory and autoimmune diseases.

Antibodies, Monoclonal↗
PubMed1988

Immunological significance of Mycobacterium leprae cell walls.

Cell walls of Mycobacterium leprae, prepared by differential solvent extraction, were shown to contain arabinogalactan, mycolates, and peptidoglycan. In addition, amino acid analysis revealed the unexpected presence of large amounts of protein that retained potent immunological reactivity. Purified cell walls stimulated proliferation of T cells from tuberculoid, but not from lepromatous leprosy, patients and elicited delayed-type hypersensitivity skin reactions in guinea pigs and patients sensitized to M. leprae. Analysis of the precursor frequency of antigen-reactive human peripheral T cells revealed that as many cells (approximately equal to 1/6000) proliferate to antigen contained in cell walls as to intact M. leprae. Sequential removal of mycolates and arabinogalactan resulted in a large peptidoglycan-protein complex that retained all the immunological activity. This immunological reactivity and the inherent protein were destroyed by proteolysis. Thus, cell wall protein is a major contributor to cell-mediated immune reactivity to this pathogenic mycobacterium.

Amino Acids↗
PubMed1988

T-cell subpopulations, expression of interleukin-2 receptor, and production of interleukin-2 and gamma interferon in human American cutaneous leishmaniasis.

Leukocyte subpopulations, the expression of the interleukin-2 (IL-2) receptor, and the production of IL-2 and gamma interferon (IFN-gamma) were studied in the peripheral blood mononuclear cells of American cutaneous leishmaniasis patients that had been stimulated in vitro with either leishmanial antigen or mitogen (phytohemagglutinin M). The 75 patients examined were classified as having either the localized (LCL; 66 patients), mucocutaneous (MCL; 5 patients), or the rare diffuse (DCL; 4 patients) form of the disease. Patients with DCL, who are characterized by their defective cell-mediated immune response to leishmanial antigen, failed to express the IL-2 receptor and did not produce IFN-gamma when exposed to the antigen but did so when stimulated by phytohemagglutinin M. Both LCL and MCL patients showed strong proliferative responses to leishmanial antigen; these were by far the greatest in MCL patients. Both groups had significantly increased IL-2 receptor expression and IFN-gamma production after exposure to either antigen or mitogen, and these were highest in the MCL patients. Concerning the leukocyte subpopulations evaluated (CD2, CD4, CD8, CD20, MO2), the most significant findings were a decrease of both CD4+ cells and the CD4/CD8 ratio in MCL patients compared with the other groups. Considering IL-2 production, in response to phytohemagglutinin M both MCL and LCL patients showed amounts of IL-2 comparable to those of the controls. Our results help explain the anergy of T cells from DCL patients to leishmanial antigen, which could lead to a defective production of IFN-gamma and possibly contribute to their incapacity to kill the Leishmania parasite. Concerning MCL patients, the significantly increased expression of IL-2 receptor, decreased expression of the CD4 (helper-inducer of suppression) phenotype, and elevated IFV-gamma production might partially explains the state of hypersensitivity and mucosal damage exhibited by these patients.

Adult↗
PubMed1988

Leukocyte subsets in the granulomatous response produced after inoculation with Mycobacterium leprae-BCG in lepromatous patients.

Leukocyte subsets present in the granulomatous response produced after the inoculation of a mixture of Mycobacterium leprae and BCG in lepromatous leprosy patients were characterized in situ using monoclonal antibodies and an immunoperoxidase technique. The granuloma produced after M. leprae-BCG inoculation showed a distribution pattern similar to tuberculoid granulomas. T lymphocytes bearing the CD8 phenotype (T cytotoxic/suppressor) were sequestered to the periphery of the epithelioid tubercles and T helper-inducer CD4+ lymphocytes were distributed throughout the infiltrate. Langerhans cells CD1+ were increased in the epidermis, and in dermis they were localized mainly in the mantle surrounding the granuloma. Most of the dermal infiltrate produced after the inoculation or M. leprae-BCG expresses the HLA-DR antigen. Similarly, most keratinocytes were also positive to this MHC antigen. The granulomatous response to BCG was similar to the inoculation of a mixture of M. leprae-BCG, however acid-fast bacilla were still present. The inoculation of M. leprae produced a macrophage granuloma with no clearing of the bacilla which resembles the lepromatous leprosy granuloma.

Antibodies, Monoclonal↗
PubMed1988

Serological patterns and specificity in American cutaneous leishmaniasis.

Sera from diverse clinical forms of American cutaneous leishmaniasis show remarkably different patterns of reactivity to Leishmania mexicana and L. braziliensis after absorption with these two species of Leishmania. The enhanced species specificity of absorbed sera was confirmed by reactions with well characterized reference strains. The use of pairs of enriched polyclonal sera from mucocutaneous and diffuse cutaneous leishmaniasis permits the preliminary classification of isolates in the L. mexicana or L. braziliensis complexes by a simple, inexpensive, and quantitative immunoassay.

Animals↗
PubMed1987

Immunotherapy versus chemotherapy in localised cutaneous leishmaniasis.

In a randomised trial a combination vaccine consisting of live BCG together with killed leishmania promastigotes was compared with a standard antimonial regimen in 94 patients with localised cutaneous leishmaniasis. Three vaccinations over 32 weeks gave a similar cure rate (94%) to three 20-day courses of meglumine antimonate. In the immunotherapy group side-effects were few (5.8%) and slight whereas in the chemotherapy group they were frequent (52.4%) and often serious. Immunotherapy is a low-cost, low-risk alternative to chemotherapy in localised cutaneous leishmaniasis, applicable by primary health services in rural areas.

Adolescent↗
PubMed1987

Gamma interferon production induced by antigens in patients with leprosy and American cutaneous leishmaniasis.

In this study, we measured gamma interferon production in mononuclear cell cultures from patients with diverse forms of leprosy and American cutaneous leishmaniasis. We studied patients with lepromatous, borderline lepromatous, borderline, and borderline tuberculoid forms of leprosy, as well as a Mitsuda-negative contact. In leishmaniasis we studied patients with localized cutaneous, mucocutaneous, and diffuse cutaneous forms of the disease. High correlation was observed between gamma interferon production and lymphocyte proliferation assays in both diseases. Resistant forms of both diseases showed significant reactivity, while the severe progressive forms were characterized by insignificant responses in both assays. Localized cutaneous leishmaniasis is characterized by variability in gamma interferon production, which may be of prognostic value in longitudinal studies.

Cells, Cultured↗
PubMed1987

Immunosuppression and cellular immunity reactions in leprosy patients treated with a mixture of Mycobacterium leprae and BCG.

Suppressor reactivity was studied in a group of leprosy patients before and after immunotherapy with a mixture of Mycobacterium leprae and BCG. The treatment increases the responses in lymphocyte transformation tests to levels which are comparable to those observed in BT-TT patients and reduces suppressor activity. The soluble extract of M. leprae appears to be more sensitive than purified intact bacilli in the lymphocyte transformation tests, but this preparation did not induce suppressor reactivity with the regularity observed when using a Dharmendra preparation.

BCG Vaccine↗
PubMed1987

Mononuclear cell subpopulations and infiltrating lymphocytes in erythema dyschromicum perstans and vitiligo.

Erythema dyschromicum perstans (EDP) and vitiligo are two cutaneous pigmentary dermatoses of unknown etiology. In the present study, the leukocyte infiltrates in the affected skin of EDP and vitiligo patients were studied using the avidin-biotin (ABC) immunoperoxidase technique and monoclonal antibodies which recognise the following mononuclear cell subgroups: T-suppressor/cytotoxic (CD8-Leu-2), T-helper (CD4 = OKT4), T-suppressor + macrophages (Leu-15), Pan T (CD3 = Leu-4), macrophages (Leu-M3) and Langerhans cells (CD1 = Leu-6), and other cellular markers such as Ia antigens and the Interleukin-2 receptor (CD25 = TAC). The immunocytochemical analysis showed a selective accumulation of CD3+, CD8+, Leu-15-, T-cytotoxic cells in the epidermis of both EDP and early lesions of vitiligo. In addition, an increase in the number of epidermal Langerhans cells (CD1+) was observed in some cases of EDP and vitiligo. The CD4/CD8 ratios in affected and uninvolved skin for both disorders were not significantly different, although values lower than unity were only observed in the infiltrates of affected skin. Ia antigen positivity was observed in the dendritic cells of the dermis and epidermis, as well as in most of the lymphoid cells within the infiltrates for both diseases. Macrophages (Leu-M3) in EDP dermal infiltrates were generally found adjacent to extracellular melanin pigment. Lymphocytes expressing TAC (CD25) surface antigens were also present in the dermal infiltrates. These morphological observations suggest a possible immune cell participation in the dyschromia of such cutaneous disorders.

Adult↗
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

Density of epidermal Langerhans cells in psoriasis patients treated with an aromatic retinoid (RO 10-9359). An immunoperoxidase study using anti-T6 and anti-Ia monoclonal antibodies.

Immunocytochemical techniques using antibodies to the specific T6 and Ia (Major Histocompatibility Complex, class II, human HLA-Dr) antigens were used to determine the densities of epidermal Langerhans cells (LC) in psoriasis patients treated with the aromatic retinoid RO 10-9359. Fourteen patients were treated with the aromatic retinoid and were skin biopsied before, during and after therapy. Two psoriasis patients receiving PUVA (systemic 8-methoxypsoralen + UVA irradiation) were included in the study. The results showed an increase in LC numbers during aromatic retinoid administration, which coincided with an improvement in the clinical severity of the lesions. At the end of retinoid administration the LC numbers were similar to those found in the initial psoriatic plaques. The density of Ia+ LC, in comparison with T6+ LC in the epidermis of psoriatic plaques were significantly different. Dendritic and non-dendritic Ia+ cells were also observed in the dermis of the plaques. Unlike aromatic retinoid treated patients, PUVA treated patients showed a decrease of both T6+ and Ia+ epidermal LC by the middle of therapy, a total absence of immunoreaction by the end of therapy, and a return to normal skin values a few weeks after treatment. This immunocytochemical study helps in distinguishing between dendritic and other possible Ia-expressing cells from the infiltrate that may penetrate the epithelium. These results do not conclusively demonstrate the role of LC in the pathogenesis of psoriasis. Other factors, such as the interrelationship with other immune response cell types and alterations in the lymphokine cascade may be important.

Adult↗
PubMed1985

HLA-linked control of predisposition to lepromatous leprosy.

In a study of the relation between HLA and lepromatous leprosy, HLA haplotype segregation was analyzed in 28 families with multiple cases of different types of leprosy. The inheritance of HLA-DR2, HLA-DR3, and HLA-MT1, which had previously been shown to be associated with susceptibility to leprosy or with a leprosy type, was analyzed separately. Segregation occurred in a significantly nonrandom fashion in both polar tuberculoid leprosy and lepromatous leprosy. This finding indicated HLA-encoded control of a predisposition to both of these forms of the disease. In both cases the segregation observed among healthy siblings was random. Thus, susceptibility to leprosy per se is probably not controlled by HLA-linked genes. HLA-DR3 was inherited preferentially by children with polar tuberculoid leprosy rather than lepromatous disease (P = .02), and HLA-MT1 was inherited preferentially by children with lepromatous leprosy (P = .04). The results confirmed the association of these genetic markers with leprosy type.

Female↗
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↗