Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation

Nat Immunol. 2004 Apr;5(4):435-42. doi: 10.1038/ni1044. Epub 2004 Mar 7.


CD28 costimulation is essential for CD4(+) T cell proliferation, survival, interleukin 2 (IL-2) production and T helper type 2 development. To define the nature of the signals that may drive different T cell responses, we have done a structure-function analysis of the CD28 cytoplasmic tail in primary T cells. CD28-mediated T cell proliferation and IL-2 production did not require a particular cytoplasmic domain. In contrast, IL-4 production was driven by the cooperative activity of specific motifs within the CD28 cytoplasmic tail. Using a gene-complementation approach, we provide evidence that one component of this T helper type 2 differentiation signal was mediated by 3-phosphoinositide-dependent protein kinase 1. Thus, different mechanisms underlie the induction of distinct T cell functional responses by CD28.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Animals
  • CD28 Antigens / genetics
  • CD28 Antigens / physiology
  • Cell Differentiation / physiology*
  • Gene Transfer Techniques
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Th2 Cells / physiology*


  • CD28 Antigens
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases