scholarly journals Human Interleukin‐12 Enhances Interferon‐γ–Producing Influenza‐Specific Memory CD8+Cytotoxic T Lymphocytes

1999 ◽  
Vol 180 (5) ◽  
pp. 1477-1486 ◽  
Author(s):  
Innocent N. Mbawuike ◽  
Kohtaro Fujihashi ◽  
Simonetta DiFabio ◽  
Shigetada Kawabata ◽  
Jerry R. McGhee ◽  
...  
1998 ◽  
Vol 89 (2) ◽  
pp. 192-198 ◽  
Author(s):  
Takeshi Hanagiri ◽  
Ichiro Yoshino ◽  
Mitsuhiro Takenoyama ◽  
Tomoko So ◽  
Hiroshi Fujie ◽  
...  

2015 ◽  
Vol 99 (5) ◽  
pp. 735-747 ◽  
Author(s):  
Ann J. Ligocki ◽  
Joseph R. Brown ◽  
Jerry Y. Niederkorn

1998 ◽  
Vol 95 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Ajit LALVANI ◽  
Adrian V. S. HILL

1. Mycobacterium tuberculosis and the liver stage of Plasmodium falciparum are intracellular pathogens which are potentially susceptible to cytotoxic T-lymphocytes, a crucial component of the protective immune response to viral infections. Evidence from animal models points to a protective role for cytotoxic T-lymphocytes against M. tuberculosis and P. falciparum, but cytotoxic T-lymphocytes specific for these pathogens have been difficult to identify in man. 2.Using a reverse immunogenetic approach, candidate epitopes from selected antigens of P. falciparum and M. tuberculosis were used to detect peptide-specific cytotoxic T-lymphocyte responses in individuals exposed to these pathogens. Cytotoxic T-lymphocyte activity was detected by the 51Cr release cytotoxicity assay and a sensitive ELISPOT assay for single-cell interferon-γ release. 3.In naturally exposed, partially immune Africans in The Gambia, eight largely conserved cytotoxic T-lymphocyte epitopes in P. falciparum, restricted by several different HLA class I alleles, were identified. Several epitopes were also recognized in Tanzanians and cytotoxic T-lymphocytes recognized endogenously processed antigen. 4.In tuberculosis patients with HLA-B52, a CD8+ cytotoxic T-lymphocyte epitope was identified in ESAT-6, a secreted antigen specific for M. tuberculosis complex but absent in BCG. Cytotoxic T-lymphocytes exhibited HLA-B52-restricted peptide-specific interferon-γ release and lytic activity and recognized endogenously processed antigen. 5.These studies demonstrate that CD8+ cytotoxic T-lymphocytes specific for mycobacterial and protozoal antigens are induced during natural infections in humans. The identification of these T-cells endorses current strategies to develop cytotoxic T-lymphocyte-inducing vaccines against P. falciparum and M. tuberculosis and highlights candidate antigens for inclusion in subunit vaccines.


Gut ◽  
1998 ◽  
Vol 43 (5) ◽  
pp. 620-628 ◽  
Author(s):  
G Monteleone ◽  
T Parrello ◽  
F Luzza ◽  
F Pallone

Background/Aim—Interleukin (IL) 12 is involved in the mucosal response during intestinal inflammation but its role is not fully understood. The response of human lamina propria T lymphocytes (T-LPL) to IL-12 in terms of interferon γ (IFN-γ) release and proliferation was investigated, exploring whether IL-15 and IL-7 cooperate with IL-12. The role of accessory molecules (CD2 and CD28) was also investigated.Methods—Unstimulated and phytohaemagglutinin preactivated T-LPL cultures were incubated with or without the initial addition of cytokines, anti-CD2 or anti-CD28 antibodies. IFN-γ mRNA was detected by reverse transcriptase polymerase chain reaction, and protein secretion was measured by enzyme linked immunosorbent assay (ELISA).Results—IFN-γ mRNA was induced in T-LPLs by IL-12 and IL-15 but not IL-7, whereas IFN-γ was measured only in IL-12 stimulated T-LPL cultures. IL-12 induced IFN-γ release was not abrogated by neutralising anti-IL-2 antibody or by cyclosporin A. IL-12 synergised with either anti-CD2 or anti-CD28 antibodies in inducing IFN-γ synthesis. In preactivated T-LPLs, IL-7 enhanced IFN-γ release induced by both IL-12 and anti-CD2, whereas IL-15 potentiated only IL-12 induced IFN-γ synthesis. IL-12 did not induce proliferation of either unstimulated or preactivated T-LPLs and it did not enhance the CD2/CD28 stimulated T-LPL proliferative response. No transcript for IL-12 receptor β1 subunit was detected in freshly isolated and activated T-LPLs whereas the β2subunit mRNA was consistently found in T-LPL samples.Conclusions—IL-12 induces human T-LPLs to produce and release IFN-γ, and IL-15 and IL-7 cooperate with IL-12 in expanding the IFN-γ mucosal response.


2004 ◽  
Vol 78 (1) ◽  
pp. 206-215 ◽  
Author(s):  
Michael S. Seaman ◽  
Fred W. Peyerl ◽  
Shawn S. Jackson ◽  
Michelle A. Lifton ◽  
Darci A. Gorgone ◽  
...  

ABSTRACT Vaccine-elicited cytotoxic T lymphocytes (CTL) should be long-lived memory cells that can rapidly expand in number following re-exposure to antigen. The present studies were initiated to analyze the ability of plasmid interleukin-12 (IL-12) to augment CTL responses in mice when delivered during the peak phase of an immune response elicited by a plasmid human immunodeficiency virus type 1 gp120 DNA vaccine. Delivery of plasmid IL-12 on day 10 postimmunization resulted in a robust expansion of gp120-specific CD8+ T cells, as measured by tetramer, gamma interferon ELISPOT, and functional-killing assays. Interestingly, this delayed administration of plasmid IL-12 had no significant effect on antigen-specific CD4+-T-cell and antibody responses. Phenotypic analyses suggested that administration of plasmid IL-12 near the time of the peak CTL response activated and expanded antigen-specific effector cells, preventing their loss through apoptosis. However, this IL-12-augmented population of gp120-specific CD8+ T cells did not efficiently expand following gp120 boost immunization, suggesting that these effector cells would be of little utility in expanding to contain a viral infection. Analyses of the phenotypic profile and anatomic distribution of the plasmid IL-12-augmented CTL population indicated that these lymphocytes were primarily effector memory rather than central memory T cells. These observations suggest that CTL-based vaccines should elicit central memory rather than effector memory T cells and illustrate the importance of monitoring the phenotype and functionality of vaccine-induced, antigen-specific CTL.


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