Antigen-specific activation thresholds of CD8+ T cells are independent of IFN-I-mediated partial lymphocyte activation
Date
2010
Authors
Wijesundara, Danushka
Kumar, Sheetal
Alsharifi, Mohammed
Mullbacher, Arno
Regner, Matthias
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
Type-I IFN (IFN-I) are highly pleiotropic cytokines known to modulate immune responses and play an early central role in mediating antiviral defenses. We have shown that IFN-I mediate transient up-regulation of a distinct subset of lymphocyte surface activation markers on both B and T cells in vivo independent of cognate antigen: a state referred to as 'partial lymphocyte activation'. Here we investigated in vitro the possibility that partial lymphocyte activation may serve to lower the antigen-specific activation thresholds for T cells. We found that the kinetics of Ca2+ flux in T cells responding to TCR cross-linking was not enhanced in partially activated T cells. Furthermore, following TCR stimulation with anti-cluster of differentiation (CD) 3ε, a lower proportion of partially activated than naive T cells proliferated. In contrast, the proliferation of partially activated and naive ovalbumin peptide (OVAp, SIINFEKL) specific CD8+ T cells (OT-I CD8+ T cells) was similar when stimulated with OVAp. Surprisingly, using an enzyme-linked immunospot (ELISPOT) assay for IFN-γ secretion, we found that a higher number of partially activated OT-I CD8+ T cells expressed effector functions than did naive OT-I CD8+ T cells. This is most readily explained by an increased survival of activated antigen-specific CD8+ T cells from a pool of partially activated T cells than naive T cells. Overall, when examining the effects of early (Ca2+ flux), intermediate (proliferation) or late events (IFN-γ secretion) of T-cell activation, we found that partial activation promotes the survival but does not alter the antigen-specific activation thresholds of CD8+ T cells.
Description
Keywords
Keywords: calcium ion; CD69 antigen; CD86 antigen; gamma interferon; interferon; ovalbumin; polyclonal antibody; T lymphocyte receptor; animal cell; animal experiment; antigen specificity; article; CD25+ T lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; cell diff Ca2+; IFN; IFN-?; Proliferation; R-IFN-ß
Citation
Collections
Source
International Immunology
Type
Journal article
Book Title
Entity type
Access Statement
License Rights
Restricted until
2037-12-31