Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation.
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.
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California 94143, USA.
Pietro G
PG
Andres
Kimberly C
KC
Howland
Ajay
A
Nirula
Lawrence P
LP
Kane
Luke
L
Barron
Douglas
D
Dresnek
Ali
A
Sadra
John
J
Imboden
Arthur
A
Weiss
Abul K
AK
Abbas
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D018014:Gene Transfer Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000502:physiology*
D018106:CD28 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases