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Koenig A.,Vermont Center for Immunology and Infectious Diseases | Koenig A.,University of Vermont | Buskiewicz I.A.,Vermont Center for Immunology and Infectious Diseases | Buskiewicz I.A.,Åbo Akademi University | And 12 more authors.
Journal of Biological Chemistry | Year: 2014

Background: c-FLIPL is a regulator of caspase-8 activity in T lymphocytes. Results: Caspase-8 activity is lost upon deletion of c-FLIPL. p43FLIP rescues caspase-8 activity through Raf1, TRAF2, and RIPK1 association, augmenting ERK and NF-κB pathways. Conclusion: The FLIPL cleavage product p43FLIP promotes activation of pathways involved with T cell growth. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Rincon M.R.,University of Vermont | Rincon M.R.,Vermont Center for Immunology and Infectious Diseases | Oppenheimer K.,University of Vermont | Bonney E.A.,University of Vermont | Bonney E.A.,Vermont Center for Immunology and Infectious Diseases
International Journal of Biological Sciences | Year: 2012

Environmental factors likely regulate neonatal immunity and self-tolerance. However, evi-dence that the neonatal immune system is suppressed or deviated is varied depending on the antigen and the timing of antigen exposure relative to birth. These disparate findings may be related to the availability of the appropriate antigen presenting cells but also point to the possibility of homeostatic changes in non-lymphoid cells in the relevant lymphoid tissues. Here we show that, while leukocytes are the most abundant cell population present in spleen during the first 4-5 days after birth, a massive accumulation of nucleated immature erythroid population in the spleen takes places on day 6 after birth. Although the relative frequency of these immature erythorid cells slowly decreases during the development of neonates, they remain one of the most predominant populations up to three weeks of age. Importantly, we show that the immature erythroid cells from neonate spleen have the capacity to modulate the differentiation of CD4 T cells into effector cells and provide a bias towards a Th2 type instead of Th1 type. These nucleated erythroid cells can produce cytokines that participate in the Th2/Th1 balance, an important one being IL-6. Thus, the selective accumulation of im-mature erythroid cells in the spleen during a specific period of neonatal development may explain the apparent differences observed in the type(s) of immune responses generated in infants and neonates. These findings are potentially relevant to the better management of immune deficiency in and to the design of vaccination strategies for the young. © Ivyspring International Publisher.

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