Purified Protein Derivative Of Mycobacterium Tuberculosis Research Articles

HIV Antigen-Reactive T Cells Detected by Antigen-Induced Interferon γ Secretion

The T cell repertoire to human immunodeficiency virus (HIV) was studied in HIV-infected patients of different clinical stages by the detection and enumeration of cells that secreted interferon gamma (IFN-gamma) in short-term cultures of blood mononuclear cells after stimulation in vitro with the HIV recombinant antigens pB1, p121, p24-15, gp160bac, and the HIV V3 loop peptide. T cell reactivities to cytomegalovirus (CMV) and Mycobacterium tuberculosis-purified protein derivative (PPD) were examined in parallel. Among 29 patients with HIV infection, 48% had blood cells recognizing one or more of the five HIV antigens. The mean numbers of HIV antigen-reactive T cells varied between 1/approximately 6000 blood cells for pB1 and 1/approximately 20,000 cells for p24-15. None of the five HIV antigens studied was identified as an immunodominant T cell epitope in HIV infection. T cells from 20% of the patients responded to all five HIV antigens in parallel, but the antigen preferentially recognized varied from patient to patient. Those with more advanced disease had a tendency to lower numbers of HIV antigen-reactive T cells. Most HIV-infected patients had both CMV- and PPD-reactive T cells, but numbers were significantly lower in more advanced disease. It should be possible to adopt the present method to evaluate fine specificities of the T cell repertoire to other antigens and to study the involvement of other cytokines besides IFN-gamma, for example, the Th2 cell-related cytokine interleukin 4.

Activation of human blood lymphocytes by house dust mite protein and Mycobacterium tuberculosis purified protein derivative: effects of interferon-gamma, interleukin-4, dexamethasone and cyclosporin A.

Peripheral blood mononuclear cells (PBMC) from nonatopic donors sensitive to Mycobacterium tuberculosis purified protein derivative (PPD) and from atopic donors sensitive to PPD and house dust mite antigen (HDM), were stimulated in vitro to proliferate in response to exogenous IL-2. In the presence of exogenous IFN-gamma, the response of cells from atopic donors to PPD was either unaffected or slightly enhanced, whereas the response to HDM was inhibited in a dose-dependent manner. The response of cells from nonatopic donors to PPD remained unchanged or was only slightly inhibited and this was not dose-dependent. Exogenous IL-4 did not reverse the inhibitory effects of IFN-gamma and a neutralizing antibody to IL-4 did not inhibit the proliferative response of cells to HDM and IL-2. Dexamethasone inhibited the IL-2-mediated response of cells from atopic donors stimulated with HDM, whereas the IL-2-mediated response of cells induced by PPD was either unchanged or stimulated by dexamethasone. Cyclosporin A inhibited the response of cells to both HDM and PPD. These results suggest that IFN-gamma can exert a selective effect on the response of T lymphocytes to different antigens and that it is possible to identify compounds able to regulate this activity.

Evidence of Previous Infection with Mycobacterium avium-Mycobacterium intracellulare Complex among Healthy Subjects: An International Study of Dominant Mycobacterial Skin Test Reactions

Skin tests with 0.1 mL of intermediate-strength Mycobacterium tuberculosis purified protein derivative (PPD) and 0.1 mL of Mycobacterium avium sensitin were conducted on 484 healthy subjects from diverse geographic sites. Reactions of > or = 5 mm to one antigen that exceeded the reaction to the other by > or = 3 mm were considered M. avium- or PPD-dominant. PPD-dominant reactions were more frequent at sites where routine Bacille Calmette-Guérin immunization is done or where there are high rates of tuberculosis: New Hampshire, 2%; Boston, 7%; Finland, 14%; Trinidad, 26%; and Kenya, 28%. However, rates of M. avium-dominant reactions ranged from 7% to 12% at all sites. Analysis of dominant reactions based on a more stringent 10-mm minimum reaction size showed similar trends. These data suggest that exposure to MAC is similar in developed and developing countries but that broad mycobacterial immunity is greater in developing countries and may contribute to the lower rates of disseminated MAC infections in AIDS in these areas.

Cell mediated immunity in Chagas' disease: Trypanosoma cruzi antigens induce suppression of the in vitro proliferative response of mononuclear cells

The partial suppression of the cell-mediated immune response by Trypanosoma cruzi antigens in patients with Chagas' disease is demonstrated in a costimulation assay with T. cruzi antigens and Mycobacterium tuberculosis purified protein derivative (PPD) or Tetanus toxoid (TT). Mononuclear cells from 13 patients with chagasic infection without evidence of heart disease, 10 patients with chagasic cardiomyopathy and 7 healthy blood bank donors were stimulated with antigen A (autoclaved epimastigotes), PPD, TT, PPD + A, PPD + TT and TT + A. The average percentage of suppression induced by costimulation of mononuclear cells with PPD and antigen A was 47.1% in patients with chagasic infection without heart disease (INF), 38.8% in patients with chagasic cardiomyopathy (CDM) and 23.3% in healthy controls. Similar values were observed when living trypomastigotes were used. A costimulatory study with PPD and TT, PPD and A and TT and A was carried out in 8 patients with chagasic infection, in order to evaluate the possibility that this difference could be due to a nonspecific inhibitory effect. The mean suppression induced by TT + PPD was -8.9, with TT + A was 52.7 and with PPD + A was 50.1. The data reported show that T. cruzi antigens induce a specific suppression of the proliferative response of mononuclear cells, that might be relevant to the persistence of the parasite in the host.

Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection

Capacity to produce interleukin-2 (IL-2) was measured in haemophiliacs from a well-defined treated cohort. Patients were selected on the basis of HIV-1 antibody status, mean annual dose of clotting factor and liver disease severity. T-cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured. Haemophiliacs had reduced IL-2 production, independent of HIV-1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV-1 antibody positive patients reduced levels correlated with PPD proliferative responses (r = 0.6, P = 0.04) and CD8 + ve (r = 0.5, P = 0.05) but not CD4 + ve cell numbers (r = 0.3, P = 0.2). No such correlations were seen in HIV-1 antibody negative patients. Reduced IL-2 production in HIV-1 antibody negative haemophiliacs was due to a qualitative defect. In HIV-1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV-1 positive patients.

Tubulointerstitial nephritis induced in the Brown Norway rat with chaotropically solubilized bovine tubular basement membrane: The model and the humoral and cellular responses

Doses of as little as 50 μg of a soluble chaotropic extract of bovine tubular basement membrane (Bov-KBr-TBM) with adjuvants induced anti-TBM antibodies and tubulo-interstitial nephritis (TIN) in Brown Norway (BN) rats. The lesion was shown by renal histology, by deposition of IgG and C3 along TBM, and in terms of the humoral and cellular immune responses to compare to that produced by the standard immunization (particulate bovine TBM) for this model of TIN in BN rats. More than half of the mononuclear cells in kidneys of BN rats with TIN bore various T-cell antigens (monoclonal antibodies W3-13, W3-25, and OX-8), and most of the infiltrating cells were positive for Ia (monoclonal antibody OX-6) by indirect immunofluorescence. Purified suspensions of these mononuclear infiltrates were prepared by using Ficoll-Hypaque gradients and the fluorescence-activated cell sorter (FACS) to eliminate renal tubular epithelial cells. The purified mononuclear cells, cultured for 5 days, incorporated thymidine in response to concanavalin A (Con A), Mycobacterium tuberculosis purified protein derivative, and Bov-KBr-TBM but not in response to a variety of autologous renal antigens. After culture for 5 days in Bov-KBr-TBM and Con A supernatant, lymph node cells (LNC) from Bov-KBr-TBM-immunized BN rats passively transferred TIN to naive BN rats. Although no cells reactive with autologous renal antigens were detected in the renal infiltrates, the transfer of disease with propagated LNC suggests that elements of the cellular immune system, in addition to anti-TBM antibody, contribute to the generation of this BN-TIN.

The Role of Nontuberculous Mycobacterial Skin Test Antigens in the Diagnosis of Mycobacterial Infections

A retrospective study of 212 patients with mycobacterial infection was conducted to determine intradermal reactivity to five tuberculin units (TU) of purified protein derivative of Mycobacterium tuberculosis (PPD-S), and purified protein derivatives (PPDs) derived from non-tuberculous mycobacteria. PPDs B, Y, A, G, and F were used. The study included 138 patients with Mycobacterium tuberculosis infection, and 74 with proved nontuberculous mycobacterial infection. Eight possible patterns of skin test reactivity were discerned using PPD-S, PPD-B, and PPD-Y. In this population, selection of the largest skin test reaction within any one pattern correlated with the infecting organism in 87 per cent of the cases. Use of PPD-A, PPD-G, and PPD-F did not increase diagnostic capability. We conclude that differential skin testing with PPD-S, PPD-B and PPD-Y, is useful in the diagnosis of mycobacterial disease.

Immunosuppression During Influenza Virus Infection

The effects of a live attenuated influenza vaccine and subsequent challenge with virulent influenza virus on the delayed hypersensitivity skin test, and the in vitro response of lymphocytes were evaluated. Volunteers were skin tested before and after administration of vaccine or placebo and challenge with PPD (a purified protein derivative of Mycobacterium tuberculosis), candida, mumps, and trichophytin, and their lymphocytes were tested for [(3)H]thymidine uptake in response to phytohemagglutin. Of eight volunteers who showed evidence of viral replication after administration of the attenuated vaccine, four had a significant diminution in their skin test response, whereas 8 of 13 volunteers infected with virulent influenza virus showed a diminution. Of the 21 volunteers who were infected with either attenuated or virulent influenza virus, 12 showed suppression of their phytohemagglutin response. None of the volunteers who were given placebo vaccine, or who showed no evidence for viral replication after immunization or challenge, had a suppression of their skin test or phytohemagglutin responses. Although most of the infected volunteers demonstrated suppression of their T-cell function, there was no evidence of a similar suppression of B-cell function.