scholarly journals Protection against Mycobacterium tuberculosisInfection by CD8+ T Cells Requires the Production of Gamma Interferon

1998 ◽  
Vol 66 (2) ◽  
pp. 830-834 ◽  
Author(s):  
Ricardo E. Tascon ◽  
Evangelos Stavropoulos ◽  
Katalin V. Lukacs ◽  
M. Joseph Colston
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Gamma Interferon ◽  
Cell Populations ◽  
Athymic Mice ◽  
Histocompatibility Complex ◽  
Cd8 Cell ◽  
Ifn Γ

ABSTRACT The role of CD8 T cells in controlling Mycobacterium tuberculosis infections in mice was confirmed by comparing the levels of growth of the organism in control, major histocompatibility complex class II knockout, and athymic mice and by transferring T-cell populations into athymic mice. By using donor mice which were incapable of making gamma interferon (IFN-γ), it was shown that IFN-γ production was essential for CD8 cell mediation of protective immunity against M. tuberculosis.

scholarly journals Effector CD8+ T Lymphocytes against Liver Stages of Plasmodium yoelii Do Not Require Gamma Interferon for Antiparasite Activity

2008 ◽  
Vol 76 (8) ◽  
pp. 3628-3631 ◽  
Author(s):  
Sumana Chakravarty ◽  
G. Christian Baldeviano ◽  
Michael G. Overstreet ◽  
Fidel Zavala
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protective Immunity ◽  
Critical Role ◽  
Plasmodium Yoelii ◽  
Gamma Interferon ◽  
Parasite Development ◽  
Wild Type ◽  
Ifn Γ

ABSTRACT The protective immune response against liver stages of the malaria parasite critically requires CD8+ T cells. Although the nature of the effector mechanism utilized by these cells to repress parasite development remains unclear, a critical role for gamma interferon (IFN-γ) has been widely assumed based on circumstantial evidence. However, the requirement for CD8+ T-cell-mediated IFN-γ production in protective immunity to this pathogen has not been directly tested. In this report, we use an adoptive transfer strategy with circumsporozoite (CS) protein-specific transgenic T cells to examine the role of CD8+ T-cell-derived IFN-γ production in Plasmodium yoelii-infected mice. We show that despite a marginal reduction in the expansion of naive IFN-γ-deficient CS-specific transgenic T cells, their antiparasite activity remains intact. Further, adoptively transferred IFN-γ-deficient CD8+ T cells were as efficient as their wild-type counterparts in limiting parasite growth in naive mice. Taken together, these studies demonstrate that IFN-γ secretion by CS-specific CD8+ T cells is not essential to protect mice against live sporozoite challenge.

scholarly journals CD8 T Cells in Old Mice Contribute to the Innate Immune Response to Mycobacterium tuberculosis via Interleukin-12p70-Dependent and Antigen-Independent Production of Gamma Interferon

2009 ◽  
Vol 77 (8) ◽  
pp. 3355-3363 ◽  
Author(s):  
Bridget Vesosky ◽  
Erin K. Rottinghaus ◽  
Craig Davis ◽  
Joanne Turner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd8 T Cells ◽  
The Elderly ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Aerosol Infection ◽  
Old Mice

ABSTRACT Elderly individuals have increased morbidity and mortality associated with infectious diseases due in part to the progressive age-associated decline in immune function. Despite this, the old mouse model of Mycobacterium tuberculosis infection has revealed a CD8- and gamma interferon (IFN-γ)-dependent early resistance to infection. In this study, we investigated the mechanism by which CD8 T cells from old mice contributed to the early immune response to M. tuberculosis. Following a low-dose aerosol infection with M. tuberculosis, CD8 T cells were identified as being a dominant source of IFN-γ expression in the lungs of old mice early after infection, before the typical onset of antigen-specific immunity. In addition, M. tuberculosis-induced IFN-γ production by CD8 T cells isolated from naïve old mice was major histocompatibility complex class I independent but was dependent on interleukin-12p70, confirming an innate role of CD8 T cells during M. tuberculosis infection. Moreover, the ability of CD8 T cells from old mice to produce increased innate IFN-γ levels in response to M. tuberculosis infection was defined as a unique function of CD8 T cells from old mice and not the aged lung environment. Finally, we have identified increased expression of SET as being one possible mechanism by which CD8 T cells from old mice produce enhanced levels of IFN-γ. Additional characterizations of the signaling events that lead to enhanced innate IFN-γ production by CD8 T cells in old mice may lead to novel strategies to further enhance or perpetuate beneficial immune responses in the elderly.

scholarly journals Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with Leishmania major

1997 ◽  
Vol 186 (7) ◽  
pp. 1137-1147 ◽  
Author(s):  
Sanjay Gurunathan ◽  
David L. Sacks ◽  
Daniel R. Brown ◽  
Steven L. Reiner ◽  
Hughes Charest ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Protective Efficacy ◽  
Dna Vaccination ◽  
Attractive Alternative ◽  
Dna Immunization ◽  
Dna Encoding ◽  
Ifn Γ

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.

scholarly journals Depletion of CD8αβ+ T Cells in Chickens Demonstrates Their Involvement in Protective Immunity towards Marek’s Disease with Respect to Tumor Incidence and Vaccinal Protection

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 557
Author(s):  
Supawadee Umthong ◽  
John R. Dunn ◽  
Hans H. Cheng
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Lymphoproliferative Disease ◽  
Tumor Formation ◽  
Marek's Disease ◽  
Control Measures ◽  
Marek’S Disease ◽  
Cell Mediated Immune Response

Marek’s disease (MD) is a lymphoproliferative disease in chickens caused by Marek’s disease virus (MDV), a highly oncogenic alphaherpesvirus. Since 1970, MD has been controlled through widespread vaccination of commercial flocks. However, repeated and unpredictable MD outbreaks continue to occur in vaccinated flocks, indicating the need for a better understanding of MDV pathogenesis to guide improved or alternative control measures. As MDV is an intracellular pathogen that infects and transforms CD4+ T cells, the host cell-mediated immune response is considered to be vital for controlling MDV replication and tumor formation. In this study, we addressed the role of CD8+ T cells in vaccinal protection by widely-used monovalent (SB-1 and HVT) and bivalent (SB-1+HVT) MD vaccines. We established a method to deplete CD8+ T cells in chickens and found that their depletion through injection of anti-CD8 monoclonal antibodies (mAb) increased tumor induction and MD pathology, and reduced vaccinal protection to MD, which supports the important role of CD8+ T cells for both MD and vaccinal protection.

scholarly journals Epitope mapping and protective immunity elicited by adenovirus expressing the Leishmania amastigote specific A2 antigen: Correlation with IFN-γ and cytolytic activity by CD8+ T cells

Vaccine ◽  
2008 ◽  
Vol 26 (35) ◽  
pp. 4585-4593 ◽  
Author(s):  
Daniela M. Resende ◽  
Bráulia C. Caetano ◽  
Míriam S. Dutra ◽  
Marcus L.O. Penido ◽  
Christiane F. Abrantes ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Epitope Mapping ◽  
Cytolytic Activity ◽  
Ifn Γ

Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3094-3101 ◽  
Author(s):  
Premlata Shankar ◽  
Melissa Russo ◽  
Brooke Harnisch ◽  
Mark Patterson ◽  
Paul Skolnik ◽  
...  
Keyword(s):  
T Cells ◽  
Reverse Transcriptase ◽  
Cd8 T Cells ◽  
Culture Medium ◽  
Significant Proportion ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Mixed Pattern

Abstract The functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN-γ after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN-γ–producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN-γ–producing cells could be detected only after IL-2 was added. IFN-γ–producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex–peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2–expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN-γ was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2.

scholarly journals CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

2005 ◽  
Vol 79 (21) ◽  
pp. 13509-13518 ◽  
Author(s):  
Jürgen Hausmann ◽  
Axel Pagenstecher ◽  
Karen Baur ◽  
Kirsten Richter ◽  
Hanns-Joachim Rziha ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Virus ◽  
Cd8 T Cells ◽  
Gamma Interferon ◽  
Wild Type ◽  
Borna Disease Virus ◽  
Ifn Γ ◽  
The Brain ◽  
Deficient Mice ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-γ) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-γ-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-γ-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-γ-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-γ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-γ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

scholarly journals Aberrant Contraction of Antigen-Specific CD4 T Cells after Infection in the Absence of Gamma Interferon or Its Receptor

2006 ◽  
Vol 74 (11) ◽  
pp. 6252-6263 ◽  
Author(s):  
Jodie S. Haring ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Gamma Interferon ◽  
Model Systems ◽  
Important Regulator ◽  
Ifn Γ ◽  
And Function ◽  
Deficient Mice

ABSTRACT Several lines of evidence from different model systems suggest that gamma interferon (IFN-γ) is an important regulator of T-cell contraction after antigen (Ag)-driven expansion. To specifically investigate the role of IFN-γ in regulating the contraction of Ag-specific CD4 T cells, we infected IFN-γ−/− and IFN-γR1−/− mice with attenuated Listeria monocytogenes and monitored the numbers of Ag-specific CD4 T cells during the expansion, contraction, and memory phases of the immune response to infection. In the absence of IFN-γ or the ligand-binding portion of its receptor, Ag-specific CD4 T cells exhibited normal expansion in numbers, but in both strains of deficient mice there was very little decrease in the number of Ag-specific CD4 T cells even at time points later than day 90 after infection. This significant delay in contraction was not due to prolonged infection, since mice treated with antibiotics to conclusively eliminate infection exhibited the same defect in contraction. In addition to altering the number of Ag-specific CD4 T cells, the absence of IFN-γ signaling also changed the phenotype of cells generated after infection. IFN-γR1−/− Ag-specific CD4 T cells reacquired expression of CD127 more quickly than wild-type cells, and more IFN-γR1−/− CD4 T cells were capable of producing both IFN-γ and interleukin 2 following Ag stimulation. From these data we conclude that IFN-γ regulates the contraction, phenotype, and function of Ag-specific CD4 T cells generated after infection.

scholarly journals Protective Immunity Induced with Malaria Vaccine, RTS,S, Is Linked toPlasmodium falciparumCircumsporozoite Protein-Specific CD4+and CD8+T Cells Producing IFN-γ

2003 ◽  
Vol 171 (12) ◽  
pp. 6961-6967 ◽  
Author(s):  
Peifang Sun ◽  
Robert Schwenk ◽  
Katherine White ◽  
Jose A. Stoute ◽  
Joe Cohen ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Malaria Vaccine ◽  
Ifn Γ

Lenalidomide Is Highly Effective in Patients with Relapsed Multiple Myeloma Following Allogeneic Stem Cell Transplantation and Increases the Frequency of CD4+FOXP3+ T Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2722-2722
Author(s):  
Monique C. Minnema ◽  
Michael van der Veer ◽  
Tineke Aarts ◽  
Maarten Emmelot ◽  
Tuna Mutis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Response Rate ◽  
Cell Populations ◽  
Ifn Γ ◽  
Grade 3

Abstract Lenalidomide has demonstrated significant clinical activity in patients with newly diagnosed and relapsed multiple myeloma (MM). Its actions are partly mediated by stimulation of cellular host anti–MM immunity. Given these potent immunomodulatory effects, we analysed whether lenalidomide could enhance graft versus tumour or graft versus Host (GvH) reactions and analysed the efficacy and toxicity of lenalidomide after allogeneic stem cell transplantation (allo-SCT). Lenalidomide 25 mg/day was given for 21 days followed by 1 week rest for a maximum of 6 cycles to 11 end-stage patients with relapsed MM following allo–SCT. Seven patients were refractory to their last treatment. From 5 patients peripheral blood was collected before, during and after lenalidomide treatment for analysis of CD4+, CD8+ T–cells, plasmacytoid and myeloid dendritic cells, regulatory T cells and NK cell populations by FACS. Also the percentage of CD4+FOXP3+ cells and IL–10 and IFN–γ producing CD4+ and CD8+ T cells were analysed by FACS. Dexamethasone 40 mg/day was added on day 1–4 and 15–18 at start of treatment in patients 2 and 5, or after 2 cycles in patients 3, 9 and 10. A high response rate was observed in these patients. Four patients developed complete (CR) or very good partial remissions (VGPR) after 1–5 treatment cycles. Three patients developed acute GvH disease (GvHD), grade 2–4. In 1 patient long lasting chronic GvHD was diminished, in another resolved. Other toxicities beyond CTC AE grade 1 were 1 patient with grade 3 diarrhoea, 1 with grade 3 muscular pain and 1 patient with grade 4 pulmonary embolism. There were 2 patients with leukocytopenia grade 3 and 4 and 2 patients with thrombocytopenia grade 2 and 3. Comprehensive immunomonitoring of 2 poor responders with stable disease (SD) or minimal response (MR) and 3 responders revealed generally no significant changes in dendritic cell populations, CD4+ and CD8+ T cells, CD56dim, CD56high and invariant NK cells. In 4/5 patients lenalidomide increased the frequency of IFN–γ producing CD4+ and CD8+ T cells. In 3/5 patients there was a decrease in the percentage of IL–10 producing CD8+ and CD4+ T cells. Remarkably, in 4/5 patients lenalidomide treatment induced a strong increase in the frequency of CD4+FOXP3+ T cells, which are considered to represent natural regulatory T cells (Tregs). In conclusion, our results reveal for the first time the potent effects with limited toxicity of lenalidomide in the allo–SCT setting with a response rate in 9 of 11 patients. In 4 of 5 patients tested we demonstrated an increase in Tregs and IFN–γ producing T cells, indicating that the action of lenalidomide is associated with immunomodulatory events involving both effector and Treg cell populations. Nr Age/Sex Refractory to last treatment Max Response/nr cycli GvHD FOXP3♣ IFNγ♣ IL-10♣ 1 62/F yes PR/2 BOS↓ nd nd nd 2 67/F yes PR/2 no nd nd nd 3 44/M yes PR/2 no 2,5↑ 3↑ 2↓ 4 62/F yes CR/4 no 0,3↓ 0 0 5 49/M yes PR/1 BOS = nd nd nd 6 64/M no PR/2 no nd nd nd 7 64/M no CR/4 acute gr 2, chronic↓ nd nd nd 8 56/F* yes VGPR/1 acute gr 4 5↑ 5↑ 2↑ 9 43/M no SD/2 no 5↑ 2↑ 2↓ 10 66/M yes VGPR/5 no nd nd nd 11 63/M† yes MR/1 acute gr 3 6↑ 2↑ 3↓

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