المؤلفون: Kidzeru, Elvis, Gasper, Melanie A, Shao, Danica, Edlefsen, Paul T, Lejarcegui, Nicholas, Havyarimana, Enock, Urdahl, Kevin, Gantt, Soren, Horton, Helen, Jaspan, Heather, Gervassi, Ana

المصدر: Journal of Leukocyte Biology ; volume 110, issue 5, page 939-950 ; ISSN 0741-5400 1938-3673

مصطلحات موضوعية: Cell Biology, Immunology, Immunology and Allergy

الوصف: The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year. MDSC frequencies were quantified, and immune responses to the childhood vaccines Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), and combination diphtheria, tetanus, and pertussis (dTaP) were measured by Ag-specific CD4+ T cell proliferation and interferon gamma (IFN-γ) production. Vaccine-specific Ab responses to HepB, dTaP, and Haemophilus influenzae type b (Hib) were quantified via Enzyme-Linked Immunosorbent assay (ELISA). MDSC frequency in mother-infant pairs was strongly correlated; the frequency of MDSC decreased in both mothers and infants during the months after delivery/birth; and by 1 year, infant MDSC frequencies rebounded to birth levels. Higher MDSC frequency at vaccination was associated with a lack of subsequent IFN-γ release in response to vaccine Ags, with the exception of BCG. With the exception of a weak, positive correlation between MDSC frequency at 6 weeks (time of initial vaccination) and peak Hepatitis B surface antigen Ab titer, Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSC) was not correlated with T cell proliferation or Ab responses in this study. The potential for MDSC-mediated suppression of vaccine Ag-specific IFN-γ responses should be explored further, and considered when evaluating candidate infant vaccines.

الإتاحة: https://doi.org/10.1002/jlb.5a0420-281rTest
https://academic.oup.com/jleukbio/article-pdf/110/5/939/49464579/jlb10875.pdfTest

المؤلفون: Gervassi, Ana, Lejarcegui, Nicholas, Dross, Sandra, Jacobson, Amanda, Itaya, Grace, Kidzeru, Elvis, Gantt, Soren, Jaspan, Heather, Horton, Helen

المصدر: PLoS One ; http://journals.plos.org/plosoneTest

مصطلحات موضوعية: T cells, Adults, Infants, Neutrophils, Blood, Immune response, Neonates, Vaccines

الوصف: Over 4 million infants die each year from infections, many of which are vaccine-preventable. Young infants respond relatively poorly to many infections and vaccines, but the basis of reduced immunity in infants is ill defined. We sought to investigate whether myeloid-derived suppressor cells (MDSC) represent one potential impediment to protective immunity in early life, which may help inform strategies for effective vaccination prior to pathogen exposure. We enrolled healthy neonates and children in the first 2 years of life along with healthy adult controls to examine the frequency and function of MDSC, a cell population able to potently suppress T cell responses. We found that MDSC, which are rarely seen in healthy adults, are present in high numbers in neonates and their frequency rapidly decreases during the first months of life. We determined that these neonatal MDSC are of granulocytic origin (G-MDSC), and suppress both CD4+ and CD8+ T cell proliferative responses in a contact-dependent manner and gamma interferon production. Understanding the role G-MDSC play in infant immunity could improve vaccine responsiveness in newborns and reduce mortality due to early-life infections.

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/11427/15323Test; http://dx.doi.org/10.1371/journal.pone.0107816Test; https://open.uct.ac.za/bitstream/11427/15323/1/Gervassi_Myeloid_derived_suppressor_cells_2014.pdfTest

الإتاحة: https://doi.org/10.1371/journal.pone.0107816Test
http://hdl.handle.net/11427/15323Test
https://open.uct.ac.za/bitstream/11427/15323/1/Gervassi_Myeloid_derived_suppressor_cells_2014.pdfTest

المؤلفون: Jacobson, Amanda, Bell, Frank, Lejarcegui, Nicholas, Mitchell, Caroline, Frenkel, Lisa, Horton, Helen

المساهمون: Sandberg, Johan K.

المصدر: PLoS ONE ; volume 8, issue 6, page e67700 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0067700Test

المؤلفون: Elahi, Shokrollah, Dinges, Warren L, Lejarcegui, Nicholas, Laing, Kerry J, Collier, Ann C, Koelle, David M, McElrath, M Juliana, Horton, Helen

المصدر: Nature Medicine ; volume 17, issue 9, page 1153-1153 ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1038/nm0911-1153aTest
http://www.nature.com/articles/nm0911-1153a.pdfTest
http://www.nature.com/articles/nm0911-1153aTest

المؤلفون: Wamalwa, Dalton, Maleche-Obimbo, Elizabeth, Bosire, Rose, Lejarcegui, Nicholas, Itaya, Grace, Kunwar, Pratima, Gasper, Melanie A

الوصف: OBJECTIVE: To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1. DESIGN: This case-control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load. METHODS: Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4 T cells. RESULTS: Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16CD56 NK cells. In addition, cases displayed less-activated CD16CD56 NK cells and CD8 T cells, based on HLA-DRCD38 costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68CD16CD56 NK cells. Finally, we detected a higher proportion of CD27CD45RA effector memory CD4 and CD8 T cells in cord blood from cases compared with controls. CONCLUSION: When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16CD56 NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status. ; a Department of Psychiatry, University of Nairobi, ; bDepartment of Mental Health, School of Medicine, Moi University, Eldoret, Kenya

العلاقة: Gasper, Melanie A., Pratima Kunwar, Grace Itaya, Nicholas Lejarcegui, Rose Bosire, Elizabeth Maleche-Obimbo, Dalton Wamalwa et al. "Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection." AIDS 28, no. 8 (2014): 1115-1124.; http://hdl.handle.net/11295/66270Test

الإتاحة: http://hdl.handle.net/11295/66270Test

المؤلفون: Gasper, Melanie A., Kunwar, Pratima, Itaya, Grace, Lejarcegui, Nicholas, Bosire, Rose, Maleche-Obimbo, Elizabeth, Wamalwa, Dalton, Slyker, Jennifer, Overbaugh, Julie, Horton, Helen, Sodora, Donald L., John-Stewart, Grace, Lohman-Payne, Barbara

المصدر: AIDS ; volume 28, issue 8, page 1115-1124 ; ISSN 0269-9370

الإتاحة: https://doi.org/10.1097/qad.0000000000000263Test

المؤلفون: Elahi, Shokrollah, Dinges, Warren L, Lejarcegui, Nicholas, Laing, Kerry J, Collier, Ann C, Koelle, David M, McElrath, M Juliana, Horton, Helen

المصدر: Nature Medicine ; volume 17, issue 8, page 989-995 ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1038/nm.2422Test
http://www.nature.com/articles/nm.2422.pdfTest
http://www.nature.com/articles/nm.2422Test

المؤلفون: Tarun, Alice S., Baer, Kerstin, Dumpit, Ronald F., Gray, Sean, Lejarcegui, Nicholas, Frevert, Ute, Kappe, Stefan H.I.

المصدر: International Journal for Parasitology ; volume 36, issue 12, page 1283-1293 ; ISSN 0020-7519

مصطلحات موضوعية: Infectious Diseases, Parasitology

الإتاحة: https://doi.org/10.1016/j.ijpara.2006.06.009Test
https://api.elsevier.com/content/article/PII:S0020751906002396?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0020751906002396?httpAccept=text/plainTest

المؤلفون: Gasper, Melanie A, Kunwar, Pratima, Itaya, Grace, Lejarcegui, Nicholas, Bosire, Rose, Maleche-Obimbo, Elizabeth, Wamalwa, Dalton, Slyker, Jennifer, Overbaugh, Julie, Horton, Helen, Sodora, Donald L, John-Stewart, Grace, Lohman-Payne, Barbara

المصدر: AIDS (02699370); 2014 May 15, Vol. 28 Issue 8, p1115-1124, 10p

المؤلفون: Elahi, Shokrollah, Dinges, Warren L., Lejarcegui, Nicholas, Laing, Kerry J., Collier, Ann C., Koelle, David M., McElrath, M. Juliana, Horton, Helen

المصدر: Nature Medicine; Aug2011, Vol. 17 Issue 8, p989-995, 7p, 1 Diagram, 5 Graphs

مصطلحات موضوعية: T cell receptors, HLA histocompatibility antigens, HIV prevention, DISEASE progression, CELL death, KILLER cells

مستخلص: Specific human leukocyte antigens (HLAs), notably HLA-B*27 and HLA-B*57 allele groups, have long been associated with control of HIV-1. Although the majority of HIV-specific CD8⁺ T cells lose proliferative capacity during chronic infection, T cells restricted by HLA-B*27 or HLA-B*57 allele groups do not. Here we show that CD8⁺ T cells restricted by 'protective' HLA allele groups are not suppressed by Treg cells, whereas, within the same individual, T cells restricted by 'nonprotective' alleles are highly suppressed ex vivo. This differential sensitivity of HIV-specific CD8⁺ T cells to Treg cell-mediated suppression correlates with their expression of the inhibitory receptor T cell immunoglobulin domain and mucin domain 3 (Tim-3) after stimulation with their cognate epitopes. Furthermore, we show that HLA-B*27- and HLA-B*57-restricted effectors also evade Treg cell-mediated suppression by directly killing Treg cells they encounter in a granzyme B (GzmB)-dependent manner. This study uncovers a previously unknown explanation for why HLA-B*27 and HLA-B*57 allele groups are associated with delayed HIV-1 disease progression. [ABSTRACT FROM AUTHOR]

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