De Novo CMV-Specific T Cell Responses In High-Risk (D+/R-) Lung Transplant Patients On Anti-Viral Prophylaxis

2012 ◽  
Author(s):  
Sharon F. Chen ◽  
Lan X. Liu ◽  
Vivan deLeon ◽  
Nirvi Mistry ◽  
David Weill ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Lung Transplant ◽  
De Novo ◽  
T Cell Responses ◽  
Cell Responses ◽  
Transplant Patients

Lung transplant patients’ T cell responses to influenza vaccine viruses between seasons

Vaccine ◽  
2008 ◽  
Vol 26 (21) ◽  
pp. 2596-2600 ◽  
Author(s):  
Mary S. Hayney ◽  
John Moran ◽  
Nicholas A. Wiegert ◽  
William J. Burlingham
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Lung Transplant ◽  
T Cell Responses ◽  
Cell Responses ◽  
Transplant Patients

scholarly journals B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

2021 ◽  
pp. annrheumdis-2021-220435
Author(s):  
Theresa Graalmann ◽  
Katharina Borst ◽  
Himanshu Manchanda ◽  
Lea Vaas ◽  
Matthias Bruhn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
De Novo ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
T Cell Expansion

ObjectivesThe monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.ConclusionsDepending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

scholarly journals Combination of Immune and Viral Factors Distinguishes Low-Risk versus High-Risk HIV-1 Disease Progression in HLA-B*5701 Subjects

2012 ◽  
Vol 86 (18) ◽  
pp. 9802-9816 ◽  
Author(s):  
Melissa M. Norström ◽  
Marcus Buggert ◽  
Johanna Tauriainen ◽  
Wendy Hartogensis ◽  
Mattia C. Prosperi ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
High Resolution ◽  
Disease Progression ◽  
T Cell Responses ◽  
Low Risk ◽  
Early Infection ◽  
Cell Responses ◽  
Cell Counts ◽  
Hiv 1

HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although rates can vary within this group. Underlying mechanisms are not fully understood but likely involve both immunological and virological dynamics. The present study investigated HIV-1in vivoevolution and epitope-specific CD8+T cell responses in six HLA-B*5701 patients who had not received antiretroviral treatment, monitored from early infection for up to 7 years. The subjects were classified as high-risk progressors (HRPs) or low-risk progressors (LRPs) based on baseline CD4+T cell counts. Dynamics of HIV-1 Gag p24 evolution and multifunctional CD8+T cell responses were evaluated by high-resolution phylogenetic analysis and polychromatic flow cytometry, respectively. In all subjects, substitutions occurred more frequently in flanking regions than in HLA-B*5701-restricted epitopes. In LRPs, p24 sequence diversity was significantly lower; sequences exhibited a higher degree of homoplasy and more constrained mutational patterns than HRPs. The HIV-1 intrahost evolutionary rate was also lower in LRPs and followed a strict molecular clock, suggesting neutral genetic drift rather than positive selection. Additionally, polyfunctional CD8+T cell responses, particularly to TW10 and QW9 epitopes, were more robust in LRPs, who also showed significantly higher interleukin-2 (IL-2) production in early infection. Overall, the findings indicate that HLA-B*5701 patients with higher CD4 counts at baseline have a lower risk of HIV-1 disease progression because of the interplay between specific HLA-linked immune responses and the rate and mode of viral evolution. The study highlights the power of a multidisciplinary approach, integrating high-resolution evolutionary and immunological data, to understand mechanisms underlying HIV-1 pathogenesis.

scholarly journals Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Maria Prendecki ◽  
Tina Thomson ◽  
Candice L Clarke ◽  
Paul Martin ◽  
Sarah Gleeson ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
T Cell Responses ◽  
Cellular Responses ◽  
Control Group ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Background Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in kidney transplant patients, assessing both serological and cellular responses. Methods 920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group. Results Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1st year post-transplant and receiving BNT162b2 was associated with seroconversion. Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83. Conclusions. Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

scholarly journals The TLR9 ligand CpG ODN 2006 is a poor adjuvant for the induction of de novo CD8+ T-cell responses in vitro

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Papagno ◽  
Nozomi Kuse ◽  
Anna Lissina ◽  
Emma Gostick ◽  
David A. Price ◽  
...  
Keyword(s):  
T Cell ◽  
De Novo ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cpg Odn ◽  
Cell Responses ◽  
Tlr9 Ligand

scholarly journals T Cell-Mediated Immune Responses to AAV and AAV Vectors

2021 ◽  
Vol 12 ◽  
Author(s):  
Hildegund C. J. Ertl
Keyword(s):  
T Cell ◽  
Gene Transfer ◽  
Immune Responses ◽  
De Novo ◽  
T Cell Responses ◽  
Adeno Associated Virus ◽  
Effector Functions ◽  
Cell Responses ◽  
High Doses

Adeno-associated virus (AAV)-mediated gene transfer has benefited patients with inherited diseases, such as hemophilia B, by achieving long-term expression of the therapeutic transgene. Nevertheless, challenges remain due to rejection of AAV-transduced cells, which in some, but not all, patients can be prevented by immunosuppression. It is assumed that CD8+ T cells induced by natural infections with AAVs are recalled by the AAV vector’s capsid and upon activation eliminate cells expressing the degraded capsid antigens. Alternatively, it is feasible that AAV vectors, especially if given at high doses, induce de novo capsid- or transgene product-specific T cell responses. This chapter discusses CD8+ T cell responses to AAV infections and AAV gene transfer and avenues to prevent their activation or block their effector functions.

scholarly journals SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection

2021 ◽  
Author(s):  
Carolyn A Cohen ◽  
Athena PY Li ◽  
Asmaa Hachim ◽  
David SC Hui ◽  
Mike YW Kwan ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
De Novo ◽  
Acute Infection ◽  
T Cell Responses ◽  
Effector Memory ◽  
Long Term Memory ◽  
Symptomatic Infection ◽  
Cell Responses ◽  
Time Post Infection

AbstractSARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults remains unclear. We quantified the SARS-CoV-2 specific T cell responses in adults and children (<13 years of age) with RT-PCR confirmed asymptomatic and symptomatic infection for long-term memory, phenotype and polyfunctional cytokines. Acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins significantly increased with age, whilst CD8+ T cell responses increased with time post infection. Infected children had significantly lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults. SARS-CoV-2-specific CD8+ T cell responses were comparable in magnitude to uninfected negative adult controls. In infected adults CD4+ T cell specificity was skewed towards structural peptides, whilst children had increased contribution of ORF1ab responses. This may reflect differing T cell compartmentalisation for antigen processing during antigen exposure or lower recruitment of memory populations. T cell polyfunctional cytokine production was comparable between children and adults, but children had a lower proportion of SARS-CoV-2 CD4+ T cell effector memory. Compared to adults, children had significantly lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses was increased in children during acute infection indicating rapid co-ordination of the T and B cell responses. However total monocyte responses were reduced in children which may be reflective of differing levels of inflammation between children and adults. Therefore, reduced prior β-coronavirus immunity and reduced activation and recruitment of de novo responses in children may drive milder COVID-19 pathogenesis.

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