scholarly journals Defective gamma interferon production in leprosy. Reversal with antigen and interleukin 2.

1983 ◽  
Vol 158 (6) ◽  
pp. 2165-2170 ◽  
Author(s):  
N Nogueira ◽  
G Kaplan ◽  
E Levy ◽  
E N Sarno ◽  
P Kushner ◽  
...  
Keyword(s):  
Concanavalin A ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Specific Antigen ◽  
Lepromatous Leprosy ◽  
Gamma Interferon ◽  
Experimental Conditions ◽  
Peripheral Blood Mononuclear ◽  
Leprosy Patients ◽  
Borderline Patients

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.

scholarly journals The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy.

1991 ◽  
Vol 173 (4) ◽  
pp. 993-1006 ◽  
Author(s):  
G Kaplan ◽  
W J Britton ◽  
G E Hancock ◽  
W J Theuvenet ◽  
K A Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Body Burden ◽  
Lepromatous Leprosy ◽  
Lymphoid Cells ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Interleukin 2

14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis

2004 ◽  
Vol 11 (3) ◽  
pp. 538-547 ◽  
Author(s):  
James A. DeVoti ◽  
Bettie M. Steinberg ◽  
David W. Rosenthal ◽  
Lynda Hatam ◽  
Andrea Vambutas ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 2 ◽  
Cytokine Expression ◽  
Gamma Interferon ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Recurrent respiratory papillomatosis (RRP) is a chronic, debilitating disease of the upper airway caused by human papillomavirus type 6 (HPV-6) or HPV-11. We describe responses of peripheral blood mononuclear cells (PBMC) and T cells from RRP patients and controls to the HPV-11 early proteins E6 and E7. PBMC were exposed in vitro to purified E6 or E7 proteins or transduced with fusion proteins containing the first 11 amino acids of the human immunodeficiency virus type 1 protein tat fused to E6 or E7 (tat-E6/tat-E7). TH1-like (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-12, and IL-18), and TH2-like (IL-4 and IL-10) cytokine mRNAs were identified by reverse transcription-PCR, and IFN-γ and IL-10 cytokine-producing cells were identified by enzyme-linked immunospot assay. These studies show that HPV-11 E6 skews IL-10-IFN-γ expression by patients with RRP toward greater expression of IL-10 than of IFN-γ. In addition, there is a general cytokine hyporesponsiveness to E6 that is more prominent for TH1-like cytokine expression by patients with severe disease. Patients showed persistent IL-10 cytokine expression by the nonadherent fraction of PBMC when challenged with E6 and tat-E6, and, in contrast to controls, both T cells and non-T cells from patients expressed IL-10. However, E7/tat-E7 cytokine responses in patients with RRP were similar to those of the controls. In contrast, E6 inhibited IL-2 and IL-18 mRNA expression that would further contribute to a cytokine microenvironment unfavorable to HPV-specific, T-cell responses that should control persistent HPV infection. In summary, E6 is the dominant inducer of cytokine expression in RRP, and it induces a skewed expression of IL-10 compared to the expression of IFN-γ.

scholarly journals T-Cell Recognition of Mycobacterial GroES Peptides in Thai Leprosy Patients and Contacts

1998 ◽  
Vol 66 (10) ◽  
pp. 4903-4909 ◽  
Author(s):  
Boosbun Chua-Intra ◽  
Somchai Peerapakorn ◽  
Nick Davey ◽  
Stipo Jurcevic ◽  
Marc Busson ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Statistical Significance ◽  
Hospital Staff ◽  
Lepromatous Leprosy ◽  
Peripheral Blood Mononuclear ◽  
Hla Dr ◽  
Tuberculoid Leprosy ◽  
Leprosy Patients ◽  
The Individual

ABSTRACT We report here the mapping of T-cell-stimulatory determinants of the GroES 10-kDa heat shock protein homologues from Mycobacterium leprae and Mycobacterium tuberculosis, which are known as major immunogens in mycobacterial infections. Peripheral blood mononuclear cells (PBMC) from treated tuberculoid leprosy or lepromatous leprosy patients and from healthy household or hospital staff contacts of the patients were cultured with 20 16-mer peptides covering the entire sequences of both M. leprae andM. tuberculosis GroES. The total number of recognized peptides was found to be the largest in family contacts, while responder frequencies to the individual tested peptides varied (5 to 80%) with specificity between the patient and contact groups. Proliferative responses to some peptides showed positive or negative associations of low statistical significance with DR and DQ alleles, though responses to most GroES peptides were genetically permissive. Notably, the sequence of the 25–40 peptide of M. leprae, but not that of M. tuberculosis, was more frequently stimulatory in tuberculoid leprosy patients than in either group of sensitized healthy contacts. This peptide bound to a number of HLA-DR molecules, of which HLA-DRB5*0101 had the strongest affinity. The epitope core binding to this allele was localized to the 29-to-37 sequence, and its key residue was localized to the M. leprae-specific glutamic acid at position 32. This epitope may be of interest for the development of a blood test- or skin test-based diagnostic reagent for tuberculoid leprosy, subject to further clinical evaluation in untreated patients.

scholarly journals Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist

2021 ◽  
Vol 9 (1) ◽  
pp. e001762
Author(s):  
Punit Upadhyaya ◽  
Johanna Lahdenranta ◽  
Kristen Hurov ◽  
Sailaja Battula ◽  
Rachel Dods ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Tumor Antigens ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cancer Therapeutics ◽  
Peripheral Blood Mononuclear ◽  
Tnf Superfamily

BackgroundIn contrast to immune checkpoint inhibitors, the use of antibodies as agonists of immune costimulatory receptors as cancer therapeutics has largely failed. We sought to address this problem using a new class of modular synthetic drugs, termed tumor-targeted immune cell agonists (TICAs), based on constrained bicyclic peptides (Bicycles).MethodsPhage libraries displaying Bicycles were panned for binders against tumor necrosis factor (TNF) superfamily receptors CD137 and OX40, and tumor antigens EphA2, Nectin-4 and programmed death ligand 1. The CD137 and OX40 Bicycles were chemically conjugated to tumor antigen Bicycles with different linkers and stoichiometric ratios of binders to obtain a library of low molecular weight TICAs (MW <8 kDa). The TICAs were evaluated in a suite of in vitro and in vivo assays to characterize their pharmacology and mechanism of action.ResultsLinking Bicycles against costimulatory receptors (e.g., CD137) to Bicycles against tumor antigens (e.g., EphA2) created potent agonists that activated the receptors selectively in the presence of tumor cells expressing these antigens. An EphA2/CD137 TICA (BCY12491) efficiently costimulated human peripheral blood mononuclear cells in vitro in the presence of EphA2 expressing tumor cell lines as measured by the increased secretion of interferon γ and interleukin-2. Treatment of C57/Bl6 mice transgenic for the human CD137 extracellular domain (huCD137) bearing EphA2-expressing MC38 tumors with BCY12491 resulted in the infiltration of CD8+ T cells, elimination of tumors and generation of immunological memory. BCY12491 was cleared quickly from the circulation (plasma t1/2 in mice of 1–2 hr), yet intermittent dosing proved effective.ConclusionTumor target-dependent CD137 agonism using a novel chemical approach (TICAs) afforded elimination of tumors with only intermittent dosing suggesting potential for a wide therapeutic index in humans. This work unlocks a new path to effective cancer immunotherapy via agonism of TNF superfamily receptors.

scholarly journals Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1

2021 ◽  
Vol 22 (15) ◽  
pp. 7988
Author(s):  
Andrea Coppola ◽  
Barbara Capuani ◽  
Francesca Pacifici ◽  
Donatella Pastore ◽  
Roberto Arriga ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Interleukin 2 ◽  
High Mobility ◽  
High Mobility Group ◽  
Low Grade ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Activation of innate immunity and low-grade inflammation contributes to hyperglycemia and an onset of Type 2 Diabetes Mellitus (T2DM). Interleukin-2 (IL-2), leptin, High Mobility Group Box-1 (HMGB-1), and increased glucose concentrations are mediators of these processes also by modulating peripheral blood mononuclear cells (PBMCs) response. The aim of this study was to investigate if HMGB-1 and IL-2 turn on PBMCs and their leptin secretion. In isolated human PBMCs and their subpopulations from healthy individuals and naïve T2DM patients, leptin release, pro-inflammatory response and Toll-like Receptors (TLRs) activation was measured. After treatment with IL-2 and HMGB1, NK (Natural Killer) have the highest amount of leptin secretion, whilst NK-T have the maximal release in basal conditions. TLR4 (TAK242) and/or TLR2 (TLR2-IgA) inhibitors decreased leptin secretion after IL-2 and HMGB1 treatment. A further non-significant increase in leptin secretion was reported in PBMCs of naive T2DM patients in response to IL-2 and HMGB-1 stimulation. Finally, hyperglycemia or hyperinsulinemia might stimulate leptin secretion from PBMCs. The amount of leptin released from PBMCs after the different treatments was enough to stimulate the secretion of IL-1β from monocytes. Targeting leptin sera levels and secretion from PBMCs could represent a new therapeutic strategy to counteract metabolic diseases such as T2DM.

Products of enteropathogenic E. coli inhibit lymphokine production by gastrointestinal lymphocytes

1996 ◽  
Vol 271 (5) ◽  
pp. G841-G848 ◽  
Author(s):  
J. M. Klapproth ◽  
M. S. Donnenberg ◽  
J. M. Abraham ◽  
S. P. James
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Enteric Bacteria ◽  
Peripheral Blood Mononuclear ◽  
Ifn Gamma ◽  
E Coli ◽  
Cd25 Expression ◽  
Lamina Propria Mononuclear Cells ◽  
Lymphokine Production

Previously we have shown that lysates of enteropathogenic Escherichia coli (EPEC) inhibit lymphokine production by mitogen-activated peripheral blood mononuclear cells (PBMCs). The aim of the present study was to determine whether products of EPEC alter lymphokine expression by gastrointestinal mucosal lymphocytes. Lysates from EPEC clones inhibited mitogen-stimulated interleukin-2 (IL-2), IL-4, IL-5, and interferon-gamma (IFN-gamma) but not IL-8 mRNA expression by lamina propria mononuclear cells isolated from surgically resected colon specimens. Inhibitory lysates did not significantly change CD25 expression on either CD4, CD8, or CD45R0 lymphocytes by flow cytometry. Bacterial supernatants of EPEC inhibited IL-2 and IL-5 protein secretion by mitogen-stimulated PBMCs. EPEC lysates inhibited IL-2 mRNA expression induced by lysates of nonpathogenic E. coli. In conclusion, EPEC contains a novel gene(s) that encodes factors that selectively inhibit IL-2, IL-4, IL-5, and IFN-gamma expression by mucosal mononuclear cells without affecting CD25 or IL-8 expression. Thus enteric bacteria can produce factors that may regulate the function of the gastrointestinal mucosal immune system.

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