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CD5-dependent CK2 activation pathway regulates threshold for T cell anergy.

CD5 activates casein kinase 2 (CK2), a serine/threonine kinase that constitutively associates with the CK2-binding domain at the end of its cytoplasmic tail. To determine the physiological significance of CD5-dependent CK2 activation in T cells, we generated a knock-in mouse that expresses a CD5 protein containing a microdeletion with selective inability to interact with CK2 (CD5ΔCK2BD). The levels of CD5 on developing and mature T cell populations from CD5ΔCK2BD mice and CD5 wild-type (WT) mice were similar. The thymus of CD5ΔCK2BD mice contained fewer double-positive thymocytes than did that of both CD5WT and CD5 knockout (KO) mice, although the numbers of all other immature and mature T cell populations were unaltered. CD5ΔCK2BD T cells hypoproliferated and exhibited enhanced activation-induced cell death when stimulated with anti-CD3 or cognate peptide in comparison with CD5WT T cells. We also found that functional CD5-dependent CK2 signaling was necessary for efficient differentiation of naive CD4+ T cells into Th2 and Th17 cells, but not Th1 cells. We previously showed that experimental autoimmune encephalomyelitis (EAE) in CD5KO mice was less severe and delayed in onset than in CD5WT mice. Remarkably, CD5ΔCK2BD mice recapitulated both EAE severity and disease onset of CD5KO mice. Increasing the immunization dose of myelin oligodendrocyte glycoprotein 35-55 peptide, a model that mimics high-dose tolerance, led to decreased severity of EAE in CD5WT mice but not in CD5KO or CD5ΔCK2BD mice. This property was recapitulated in in vitro restimulation assays. These results demonstrate that CD5-CK2 signaling sets the threshold for T cell responsiveness and is necessary for efficient generation of Th2 and Th17 cells.

Pubmed ID: 22904299

Authors

  • Sestero CM
  • McGuire DJ
  • De Sarno P
  • Brantley EC
  • Soldevila G
  • Axtell RC
  • Raman C

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

September 15, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 5K12GM088010
  • Agency: NIAID NIH HHS, Id: AI1076562
  • Agency: NCRR NIH HHS, Id: G20 RR022807-01
  • Agency: NCRR NIH HHS, Id: G20 RR025858
  • Agency: NIGMS NIH HHS, Id: K12 GM088010
  • Agency: NINDS NIH HHS, Id: NS064261
  • Agency: NIAID NIH HHS, Id: P30 AI027767
  • Agency: NIAMS NIH HHS, Id: P30 AR 48311
  • Agency: NIAMS NIH HHS, Id: P30 AR048311
  • Agency: NIAMS NIH HHS, Id: P30 AR48311
  • Agency: NCI NIH HHS, Id: P30 CA-13148
  • Agency: NIAID NIH HHS, Id: R01 AI076562
  • Agency: NINDS NIH HHS, Id: R01 NS064261
  • Agency: NIAID NIH HHS, Id: T32 AI007051
  • Agency: NIAMS NIH HHS, Id: T32 AR007450
  • Agency: NIAMS NIH HHS, Id: T32 AR07450

Mesh Terms

  • Animals
  • Antigens, CD5
  • Casein Kinase II
  • Cell Differentiation
  • Clonal Anergy
  • Encephalomyelitis, Autoimmune, Experimental
  • Enzyme Activation
  • Female
  • Gene Knock-In Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Signal Transduction
  • T-Lymphocyte Subsets
  • Th1 Cells
  • Th17 Cells
  • Th2 Cells