A Dose-dependent Requirement for the Proline Motif of CD28 in Cellular and Humoral Immunity Revealed by a Targeted Knockin Mutant

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2006 Aug 16

PMID 16908623

Citations 35

Authors

Lindzy D Friend

Dulari D Shah

Christine Deppong

Joseph Lin

Traci L Bricker

Twyla I Juehne

Christine M Rose

Jonathan M Green

Affiliations

Soon will be listed here.

Abstract

Activation of naive T cells requires the integration of signals through the antigen receptor and CD28. Although there is agreement on the importance of CD28, there remains controversy on the mechanism by which CD28 regulates T cell function. We have generated a gene-targeted knockin mouse expressing a mutation in the C-terminal proline-rich region of the cytoplasmic tail of CD28. Our analysis conclusively showed that this motif is essential for CD28-dependent regulation of interleukin 2 secretion and proliferation. In vivo analysis revealed that mutation of this motif-dissociated CD28-dependent regulation of cellular and humoral responses in an allergic airway inflammation model. Furthermore, we find an important gene dosage effect on the phenotype of the mutation and provide a mechanistic explanation for the conflicting data on the significance of this motif in CD28 function.

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