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T H Rea

Publications and source records attributed to T H Rea.

At least 55 records · Page 3Linked to original sources
PubMed1990

Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates.

We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.

Adolescent↗
PubMed1989

Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions.

The majority of T cells bear the T-cell receptor (TCR) alpha beta complex which recognizes foreign antigen peptides only in the context of self major histocompatibility complex (MHC) molecules. Such T cells function in a variety of effector roles and secrete cytokines that mediate the activation and differentiation of other cells in the immune system. Recently, a small subpopulation T cells was found to bear a distinct TCR composed of gamma and delta subunits. In man, TCR gamma delta+ cells are distributed as approximately 5 per cent of the CD3+ cells in all organized lymphoid organs as well as in the skin- and gut-associated lymphoid tissues. Although a limited number of germ-line genes encode the TCR gamma and delta subunits, extensive junctional variation particularly in the delta gene, results in unprecedented diversity for this receptor. The nature of the specificity and immunological functions of these T cells remains enigmatic. We report here that in contrast to the normal low frequency of gamma delta-bearing cells in lymphoid tissues, peripheral blood, or normal skin, the frequency is increased five to eightfold in particular granulomatous reactions of leprosy. TCR gamma delta+ lymphocyte lines from these leprosy skin lesions proliferate in vitro specifically to mycobacterial antigens. This reactivity to foreign antigens appears to require presentation in the context of self-molecules. Moreover, culture supernatants from activated gamma delta T lymphocytes induce adhesion and aggregation of bone-marrow monocytes in the presence of granulocyte monocyte-colony stimulating factor (CSF), suggesting that products of gamma delta-bearing T cells may play a role in the immune response, possibly by stimulating granuloma formation.

Epitopes↗
PubMed1989

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

Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.

Esterases↗
PubMed1989

Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis.

The study of T lymphocytes from pleural fluid and tissue of patients with tuberculous pleuritis provides an opportunity to evaluate the human immune response to infection at the site of disease activity. Therefore, we investigated the phenotype and function of CD4+ pleural fluid cells from patients with tuberculous pleuritis. Pleural fluid was enriched with CD4+CDw29+ T lymphocytes, which are thought to represent "memory" T cells. Immunoperoxidase staining of pleural tissue confirmed the predominance of CD4+CDw29+ T lymphocytes at the site of disease activity. CD4+ subpopulations were evaluated for their ability to contribute to a cell-mediated immune response against Mycobacterium tuberculosis by assaying immune function in vitro. Pleural fluid-derived CD4+CDw29+ cells, but not CD4+CDw29- lymphocytes, proliferated vigorously and produced high levels of IFN-gamma when stimulated with purified protein derivative of M. tuberculosis. CD4+CDw29+ clones produced IFN-gamma specifically in response to purified protein derivative of M. tuberculosis but not to an irrelevant Ag, tetanus toxoid. IFN-gamma levels were markedly elevated in pleural fluid, compared to peripheral blood, suggesting production of this lymphokine in vivo at the site of tissue inflammation. The sum of these data indicate that, in tuberculous pleuritis, CD4+CDw29+ cells are concentrated at the site of disease activity, produce IFN-gamma and are likely to play an important role in the local human cell-mediated immune response to M. tuberculosis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

CD2 expression and function in lepromatous leprosy.

Leprosy is a spectral disease in which clinical presentation is thought to be related to the host immune response. Previous investigations have suggested that selective unresponsiveness to Mycobacterium leprae in patients with lepromatous leprosy is due to the presence of M. leprae-specific T-suppressor cells. However, it has recently been suggested that CD2 modulation was the mechanism for the observed impaired immune response in lepromatous patients. Therefore, we studied the expression of CD2 and CD3 on lymphocytes in lepromatous skin lesions and peripheral blood mononuclear cells (PBMC). Using immunohistochemical techniques, we found that virtually all of the CD3+ cells in leprosy skin lesions expressed CD2. In addition, indirect immunofluorescence flow cytometry demonstrated that most CD3+ cells in the peripheral blood possessed the CD2 marker, suggesting that CD2 expression of T-lymphocytes is normal. T-cell activation using paired anti-T11(2) and anti-T11(3) or anti-CD3 monoclonal antibodies demonstrated similar 3H-thymidine incorporation and gamma interferon production in the PBMC of lepromatous patients in comparison with the PBMC of their contacts and tuberculoid patients. However, lepromatous PBMC did not proliferate or produce gamma interferon in response to M. leprae. Our data suggest not only that CD2 expression is normal on T lymphocytes in lepromatous leprosy skin lesions but also that CD2 expression in peripheral blood lymphocytes is functional in T-cell activation. Defective CD2 modulation does not appear to be the mechanism for specific unresponsiveness in lepromatous leprosy.

Antibodies, Monoclonal↗
PubMed1989

Leprosy.

Explore the source record for details and available documents.

Antibodies, Bacterial↗
PubMed1988

Hypercalcemia and abnormal 1,25-dihydroxyvitamin D concentrations in leprosy.

Two patients with lepromatous leprosy and hypercalcemia are presented. Serum immunoreactive parathyroid hormone and urinary cyclic adenosine monophosphate concentrations were suppressed. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were elevated in one patient and normal in the other. Urinary hydroxyproline excretion was slightly high in both patients. Hypercalcemia resolved excretion was slightly high in both patients. Hypercalcemia resolved with prednisone therapy. Abnormal 1,25-(OH)2D production and/or metabolism may play a role in the pathogenesis of hypercalcemia in some patients with leprosy.

Adult↗
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

A comparative study of testicular involvement in lepromatous and borderline lepromatous leprosy.

To measure the comparative prevalence of testicular involvement in borderline lepromatous (BL) and lepromatous (LL) leprosy patients, serum FSH, LH, and total testosterone levels were measured in 42 LL and 21 BL subjects. Serum FSH levels were elevated in 19% of BL and in 86% of LL patients. Serum LH values were increased in 10% of BL and in 79% of LL patients. Total serum testosterone values below the normal limit of 280 ng/dl were not found in BL subjects but were present in 31% (13) of the LL cases. By measuring serum free testosterone in patients with low-normal total values, one BL and an additional five LL patients could be identified as below normal limits, i.e., less than 50 pg/ml. Thus, androgen deficiency was present in 5% of BL and in 43% of LL subjects. All of these differences between the BL and LL patients were statistically significant.

Adult↗
PubMed1988

Immunohistology of tuberculous adenitis in symptomatic HIV infection.

Monoclonal antibodies and immunoperoxidase staining were used to characterize the cellular subpopulations in lymph nodes from 10 patients with tuberculous lymphadenitis, seven of whom had symptomatic human immunodeficiency virus (HIV) infection. CD4+ cells were significantly fewer in nodes of patients with HIV infection than in those of immunocompetent patients. CD8+ cells were distributed throughout the granuloma in patients with HIV infection, but confined to the periphery in normal hosts. Blastoid Ta1+ cells, putatively antigen-reactive T lymphocytes, were seen in immunocompetent patients but not in those with HIV infection, suggesting that these cells fail to mature appropriately in the latter group. The immunopathological features noted above provide preliminary evidence that the cell-mediated immune response to tuberculosis is abnormal in patients with HIV infection, and may in part explain both the severe and the unusual manifestations of tuberculosis in these individuals.

AIDS-Related Complex↗
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↗