Human Interleukin‐12 Enhances Interferon‐γ–Producing Influenza‐Specific Memory CD8<sup>+</sup>Cytotoxic T Lymphocytes

Mbawuike, Innocent N.; Fujihashi, Kohtaro; Difabio, S.; Kawabata, Shigetada; McGhee, Jerry R.; Couch, Robert B.; Kiyono, Hiroshi

doi:10.1086/315090

Cited by 30 publications

(19 citation statements)

References 48 publications

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“…We showed previously that IL-12 enhanced influenza virusspecific memory CD8 + CTL activity in humans 24,55 and recently that IL-12 with or without IL-18 augmented CTL responses in aged mice. 57,68 Other studies have demonstrated the ability of IL-12 to inhibit apoptosis and increase T cell functions.…”

Section: Effects Of Ril-12 Treatment On Ctl Responses Apoptosis and mentioning

confidence: 90%

“…First strand cDNA reverse transcription and cDNA amplification using gene specific primers were performed as previously described. 55,57 b-Actin was used as a positive control. The sense and anti-sense primer sequences used, respectively, were as follows: mb-actin, 5'-GTG GGC CGC TCT AGG CAC CAA-3' and 5'-CTC TTT GAT GTC ACG CAC GAT TTC-3'; mTNF-a: 5'-TTCTGTCTACTGAACTTCGGGGTGATCGGTCC-3' and 5' -GTAT-GAGATAGCAAATCGGCTGACGGTGTGGG-3'; mTNFRII (TNFRp75): 5'-GCAAGCACAGATGCAGTCTG-3' and 5'-GGTCAGAGCTGC-TACAGACG-3'.…”

Section: Elisa For Ifn-g and Tnf-amentioning

confidence: 99%

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Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice

et al. 2002

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Some studies have reported increased apoptosis in CD8 + T cells from aged mice. We previously demonstrated diminished virus-specific CD8 + cytotoxic T lymphocyte (CTL) activity in aged mice in comparison to young mice. The present study investigated the role of apoptosis in age-related influenza virus-specific CD8 + CTL deficiency. Splenocytes from influenza-primed aged and young mice were stimulated in vitro with virus. The CD8 + T cell/total lymphocyte ratios correlated with CTL activity and were significantly decreased and increased in aged and young mice, respectively. Fas, FasL, TNF-a and TNFR-p55 expression, measured by flow cytometry, ELISA and/or RT ± PCR, were significantly elevated in aged mice. Apoptotic CD8 + T cells (Annexin V binding) were also elevated in aged mice. IL-12 treatment increased CD8 + CTL activity and IFN-g production but did not affect apoptosis. Thus, apoptosis may contribute to reduced influenza virusspecific CD8 + T cell frequency, CTL deficiency and increased influenza disease in aging.

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Section: Effects Of Ril-12 Treatment On Ctl Responses Apoptosis and mentioning

confidence: 90%

Section: Elisa For Ifn-g and Tnf-amentioning

confidence: 99%

Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice

et al. 2002

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“…Peripheral blood mononuclear cells (PBMC) were obtained and cryopreserved as described previously (11). Viruses used in CMI assays were A/Taiwan/1/86 (H1N1), B/Panama/45/90 and the three vaccine strains.…”

Section: Assaysmentioning

confidence: 99%

“…Cytotoxicity-Assays for cytotoxic lymphocytes (CTLs) were conducted as described previously (11,12). Briefly, cryopreserved PBMCs were thawed, washed and verified as >95% viable.…”

Section: Assaysmentioning

confidence: 99%

“…The mixture was incubated in microtiter plates for four hours followed by determination of radioactivity (cpm) in a gamma counter. The percent specific cytolytic activity was calculated using a described formula (11). Lysis of ≥10% was considered significant and an increase from prevaccination levels of ≥5% at two or four weeks was considered to be a significant increase.…”

Section: Assaysmentioning

confidence: 99%

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Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

Mbawuike¹,

Zang²,

Couch³

2007

Vaccine

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To evaluate humoral (antibody) and cell mediated immune (CMI) responses, 30 healthy young adults were either given inactivated influenza vaccine with or without QS21 adjuvant. Vaccination site pain and postvaccination myalgias were greater in the QS21 group. Serum antibody increases occurred in 73 to 93% of subjects for each vaccine and antigen at 2 weeks and 4 weeks but frequencies and mean titers for the two vaccines were not different. No differences in T cell cytotoxicity were detected for either vaccine for influenza A or B infected cells. IFN-γ for both vaccine groups was increased in supernates after 3 days but not 7 days of stimulation in the cytotoxicity tests; amounts for the two vaccines were similar. To further evaluate CMI, remaining PBMCs were stimulated overnight with cells infected with each vaccine strain; an increase in spot forming cells (sfc) for Granzyme B and IFN-γ was found for all subjects and in 51 of 54 sfc tests. A slightly higher response in the Gran B test for QS21 subjects was suggested, but no clear immune response advantage was identified among healthy adults for QS21 adjuvanted influenza vaccine.

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Symptom pathogenesis during acute influenza: Interleukin‐6 and Other cytokine responses

Kaiser

Fritz

Straus

et al. 2001

Journal of Medical Virology

318

227

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In experimental human influenza infection initiated by nasal inoculation, the magnitude of viral replication, fever, and symptoms correlate with nasopharyngeal lavage fluid levels of various cytokines. Our aim was to assess these relationships in patients with naturally occurring acute influenza. Patients with culture-positive influenza illness of less than 36 hr of duration were studied. Nasopharyngeal washing were collected at enrollment and on Day 2, 4, 6 and 8 for quantitative virus isolation and IL-6, TNF-alpha, INF-alpha, INF-gamma and IL-10 determinations. Blood samples collected at entry and on Day 2 and 6 were processed to assess plasma cytokines and circulating influenza RNA. Patients received either oseltamivir or placebo for 5 days. We assessed the correlation between nasopharyngeal lavage fluid or blood levels of cytokines before treatment and viral titers, symptom severity and fever. Sixteen adult subjects (median age of 22 years) were studied. In this small group of patients no significant differences between placebo and oseltamivir patients were found in viral replication or measures of cytokines. Thus the data for all 16 subjects were pooled for analysis. At entry, influenza A viruses were cultured from nasopharyngeal washes at a median titer of 4.8 log(10)TCID(50)/ml of wash. Viral titers correlated positively with symptom score (P = 0.006) and temperature values (P < 0.001). Viral titers, fever and symptoms were highest at enrollment and fell in parallel during the subsequent days. RT-PCR assays failed to detect influenza RNA in the white blood cells from any patient. We observed a significant release, in both nasopharyngeal lavage fluid and in plasma, of IL-6, TNF-alpha, INF-alpha, INF-gamma and IL-10. At entry high IL-6 levels were detected in the nasopharyngeal lavage fluid (median 10.3 pg/ml) and plasma (median 5.1 pg/ml) of all patients. We found a positive correlation between plasma IL-6 levels and both symptom scores and temperature values (P < 0.05), as well as a positive correlation between nasopharyngeal lavage fluid levels of IL-6 and TNF-alpha and temperature (P < 0.05). We did not find significant associations between symptoms, fever and levels of INF-alpha, INF-gamma or IL-10. The magnitude of early decrease in viral titers correlated with initial levels of INF-gamma in nasopharyngeal lavage fluid (P < 0.05). Significant production of IL-6, TNF-alpha, INF-alpha, INF-gamma and IL-10 occurs in response to community acquired influenza A illness. As in experimental influenza, symptoms and fever in natural acute influenza correlate with the release of IL-6.

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

Cited by 30 publications

References 48 publications

Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice

Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice

Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

Symptom pathogenesis during acute influenza: Interleukin‐6 and Other cytokine responses

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

Cited by 30 publications

References 48 publications

Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice

Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice

Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

Symptom pathogenesis during acute influenza: Interleukin‐6 and Other cytokine responses

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Product

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