Role of Infectious Virus Expression and Immune Response in Retrovirus-Induced Oncogenesis

Some of the parameters involved in retrovirus-induced oncogenesis were analyzed in newborn mice injected with Moloney-murine leukemia virus (M-MuLV) as well as in adults who received the virus by the intraperitoneal (i.p.) or intrathymic (i.t.) route. The neonatally injected mice were permissive for both viral replication and virus-induced cell-surface antigen expression on thymus cells, peripheral T and B lymphocytes, and macrophages, whereas the M-MuLV was not present in the adult i.p. injected mice. Instead, in i.t. injected mice, the virus was expressed in thymus and peripheral T cells only, but was not detected in tail extracts as assessed by means of the UV-XC plaque assay. Lack of virus spread in adult-treated animals correlated with a prompt humoral and cellular immune response, whereas the highly viremic newborn inoculated mice showed negligible virus-specific antibody production and an extremely low frequency of splenic cytotoxic T lymphocyte precursors. Moreover, immune response in both groups of adult-treated mice efficiently prevented tumor induction by Moloney-murine sarcoma virus (M-MuSV), which has the same antigenic determinants as M-MuLV, its natural helper. In contrast, M-MuSV sarcomas grew progressively in newborn inoculated mice and killed the host. Finally, 80 % of neonatally injected mice developed lymphomas, whereas all treated adults remained free of disease for more than 15 months. These findings imply that the immune response may, in fact, prevent retrovirus-induced oncogenesis through restriction of virus replication and/or destruction of virus-infected cells.

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AUTOGENOUS IMMUNITY TO ENDOGENOUS RNA TUMOR VIRUS

Journal of Experimental Medicine ◽

10.1084/jem.139.6.1568 ◽

1974 ◽

Vol 139 (6) ◽

pp. 1568-1581 ◽

Cited By ~ 52

Author(s):

J. N. Ihle ◽

M. G. Hanna ◽

L. E. Roberson ◽

F. T. Kenney

Keyword(s):

Immune Response ◽

Leukemia Virus ◽

Polyacrylamide Gel Electrophoresis ◽

Viral Envelope ◽

Antigenic Determinants ◽

Viral Antigens ◽

Intact Virus ◽

Tumor Virus ◽

Common Antigens ◽

Antibody Levels

The viral antigenic determinants recognized in an autogenous immune response in mice against their endogenous C-type virus have been identified by SDS-polyacrylamide gel electrophoresis of immune precipitates between various sera and H3-labeled intact or disrupted AKR leukemia virus. Normal B6C3F1 [(C57BL/6 x C3H/Anf)F1] serum reacts with viral envelope antigens having mol wt of approximately 68,000, 43,000, and 17,000. In addition, minor reactions with viral antigens having mol wts of approximately 19,000 and 15,000 are demonstrable. The 68,000 and 43,000 mol wt antigens can be labeled with [3H]glucosamine and may correspond to the major viral envelope antigens M2 and M1, respectively. The antigens recognized by autogenous immune sera do not differ with respect to age of the animal, nor are they significantly different in sera from various strains of mice (BALB/c, C57BL/6, and C3H/Anf). These results suggest that the age-asociated and strain variations in the autogenous immune response, as determined by radioimmune precipitation assays against intact virus, are due to quantitative and qualitative alterations of antibody levels against common antigens.

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Ultraviolet-Light-Inactivated Cas-Br-M Murine Leukemia Virus Induces a Protective CD8+Cytotoxic T Lymphocyte Response in Newborn Mice

AIDS Research and Human Retroviruses ◽

10.1089/aid.1994.10.1695 ◽

1994 ◽

Vol 10 (12) ◽

pp. 1695-1702 ◽

Cited By ~ 9

Author(s):

M. SARZOTTI ◽

T.A. DEAN ◽

M. REMINGTON ◽

P.M. HOFFMAN

Keyword(s):

Ultraviolet Light ◽

T Lymphocyte ◽

Murine Leukemia Virus ◽

Cytotoxic T Lymphocyte ◽

Leukemia Virus ◽

Lymphocyte Response ◽

Newborn Mice ◽

Cytotoxic T Lymphocyte Response ◽

Murine Leukemia

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Immune inhibitory function of bovine CTLA-4 and the effects of its blockade in IFN-γ production

BMC Veterinary Research ◽

10.1186/s12917-019-2082-7 ◽

2019 ◽

Vol 15 (1) ◽

Author(s):

Kei Watari ◽

Satoru Konnai ◽

Naoya Maekawa ◽

Tomohiro Okagawa ◽

Yasuhiko Suzuki ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Mononuclear Cells ◽

Cytotoxic T Lymphocyte ◽

Leukemia Virus ◽

Malignant Neoplasms ◽

Dependent Manner ◽

Chronic Infections ◽

Peripheral Blood Mononuclear ◽

Ifn Γ

Abstract Background Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is known as an immune inhibitory receptor that is expressed on activated effector T cells and regulatory T cells. When CTLA-4 binds to CD80 or CD86, immunoinhibitory signals are transmitted to retain a homeostasis of the immune response. Recent studies have reported that CTLA-4 is upregulated in chronic infections and malignant neoplasms, contributing to host immune dysfunction. On the other hand, the blockade of CTLA-4 and CD80 or CD86 binding by antibody restores the immune response against these diseases. In a previous report, we indicated that the expression of CTLA-4 was closely associated with disease progression in cattle infected with the bovine leukemia virus (BLV). In this study, we established an anti-bovine CTLA-4 antibody to confirm its immune enhancing effect. Results Bovine CTLA-4-Ig binds to bovine CD80 and CD86 expressing cells. Additionally, CD80 and CD86 bind to CTLA-4 expressing cells in an expression-dependent manner. Bovine CTLA-4-Ig significantly inhibited interferon-gamma (IFN-γ) production from bovine peripheral blood mononuclear cells (PBMCs) activated by Staphylococcus enterotoxin B (SEB). An established specific monoclonal antibody (mAb) for bovine CTLA-4 specifically recognized only with bovine CTLA-4, not CD28, and the antibody blocked the binding of CTLA-4-Ig to both CD80 and CD86 in a dose-dependent manner. The bovine CTLA-4 mAb significantly restored the inhibited IFN-γ production from the CTLA-4-Ig treated PBMCs. In addition, the CTLA-4 mAb significantly enhanced IFN-γ production from CTLA-4 expressing PBMCs activated by SEB. Finally, we examined whether a CTLA-4 blockade by CTLA-4 mAb could restore the immune reaction during chronic infection; the blockade assay was performed using PBMCs from BLV-infected cattle. The CTLA-4 blockade enhanced IFN-γ production from the PBMCs in response to BLV-antigens. Conclusions Collectively, these results suggest that anti-bovine CTLA-4 antibody can reactivate lymphocyte functions and could be applied for a new therapy against refractory chronic diseases. Further investigation is required for future clinical applications.

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Altered thymic epithelial cells may be decisive for Moloney virus-induced lymphoma development

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077499 ◽

1983 ◽

Vol 41 ◽

pp. 784-785

Author(s):

U.I. Heine ◽

G.R.F. Krueger ◽

E. Munoz ◽

A. Karpinski

Keyword(s):

Epithelial Cells ◽

Leukemia Virus ◽

Light And Electron Microscopy ◽

Tumor Development ◽

Current Evidence ◽

Thymic Epithelial Cells ◽

Thymic Tissue ◽

Newborn Mice ◽

Moloney Leukemia Virus ◽

Differentiation Block

Infection of newborn mice with Moloney leukemia virus (M-MuLV) causes a T-cell differentiation block in the thymic cortex accompanied by proliferation and accumulation of prethymic lymphoblasts in the thymus and subsequent spreading of these cells to generate systemic lymphoma. Current evidence shows that thymic reticular epithelial cells (REC) provide a microenvironment necessary for the maturation of prethymic lymphoblasts to mature T-lymphocytes by secretion of various thymic factors. A change in that environment due to infection of REC by virus could be decisive for the failure of lymphoblasts to mature and thus contribute to lymphoma development.We have studied the morphology and distribution of the major thymic cell populations at different stages of tumorigenesis in Balb/c mice infected when newborn with 0.2ml M-MuLV suspension, 6.8 log FFU/ml. Thymic tissue taken at 1-2 weekly intervals up to tumor development was processed for light and electron microscopy, using glutaraldehyde-OsO4fixation and Epon-Araldite embedding.

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Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro

Nutrients ◽

10.3390/nu13020328 ◽

2021 ◽

Vol 13 (2) ◽

pp. 328 ◽

Cited By ~ 1

Author(s):

Claudio Salaris ◽

Melania Scarpa ◽

Marina Elli ◽

Alice Bertolini ◽

Simone Guglielmetti ◽

...

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Plaque Assay ◽

Immune Response Gene ◽

Intestinal Epithelial ◽

Antiviral Immune Response ◽

Qrt Pcr ◽

Anti Inflammatory

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

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Sex dependent differences in physiological ageing in the immune system of lower airways in healthy non-smoking volunteers: study of lymphocyte subsets in bronchoalveolar lavage fluid and blood

Thorax ◽

10.1136/thx.56.6.450 ◽

2001 ◽

Vol 56 (6) ◽

pp. 450-455

Author(s):

E Mund ◽

B Christensson ◽

K Larsson ◽

R Grönneberg

Keyword(s):

Immune System ◽

Bronchoalveolar Lavage ◽

Lymphocyte Subsets ◽

Antigen Expression ◽

Lavage Fluid ◽

Physiological Ageing ◽

Younger Women ◽

Cd8 Cells ◽

Age Related ◽

Surface Antigen Expression

BACKGROUNDAge related changes in the immune system have been studied frequently but a possible relation to sex has not, to our knowledge, previously been examined. The effect of age and sex on the composition of lymphocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood was therefore examined.METHODSBronchoscopy with lavage was performed in 32 healthy non-atopic, non-smoking volunteers (16 women aged 26–63 years (mean 44) and 16 men aged 23–63 years (mean 39)). Cytospin preparations for differential counts of BAL fluid cells and surface antigen expression of lymphocytes from BAL fluid and blood were analysed by flow cytometry.RESULTSMost parameters in the BAL fluid changed with age in women. The percentage of CD4+ lymphocytes increased with age from a mean of 48 (SD10)% in women aged ⩽40 years to 69 (11)% in women aged >43 years (p=0.001). The percentage of CD8+ lymphocytes tended to decrease with age and the CD4/CD8 ratio was 5.8 (1.2) in women aged >43 years compared with 2.1 (0.7) in those aged ⩽40 years (p<0.0001). Women aged >43 years differed from men aged >43 years as well as from younger subjects of both sexes with respect to CD4+ cells and CD4/CD8 ratio, and from younger women with respect to CD8+ cells. There was no age related change in the CD4/CD8 ratio in blood. No sex related differences were seen in the blood or BAL fluid of adults below the age of 40 years.CONCLUSIONSThe composition of lymphocytes with different phenotypes in the lower respiratory tract changes with age in women but not in men. This may have implications for some clinical conditions such as chronic dry cough which are observed predominantly in women.

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