Journal of Molecular Medicine

, Volume 83, Issue 4, pp 267–278

T-helper cell intrinsic defects in lupus that break peripheral tolerance to nuclear autoantigens

Review

DOI: 10.1007/s00109-004-0624-2

Cite this article as:
Datta, S.K., Zhang, L. & Xu, L. J Mol Med (2005) 83: 267. doi:10.1007/s00109-004-0624-2

Abstract

Special populations of T helper cells drive B cells to produce IgG class switched, pathogenic autoantibodies in lupus. The major source of antigenic determinants (epitopes) that trigger interactions between lupus T and B cells is nucleosomes of apoptotic cells. These epitopes can be used for antigen-specific therapy of lupus. Secondly, the autoimmune T cells of lupus are sustained because they resist anergy and activation-induced programmed cell death by markedly upregulating cyclooxygenase (COX) 2 along with the antiapoptotic molecule c-FLIP. Only certain COX-2 inhibitors block pathogenic anti-DNA autoantibody production in lupus by causing death of autoimmune T helper cells. Hence COX-2 inhibitors may work independently of their ability to block the enzymatic function of COX-2, and structural peculiarities of these select inhibitors may lead to better drug discovery and design.

Keywords

LupusAutoimmunityApoptosisAnergyImmunotherapy

Abbreviations

APC

Antigen-presenting cell

Cbl

Cassitus B lymphoma oncogene

CD40L

CD40 ligand

c-FLIP

Cellular Fas-associated death domain-like interleukin 1β converting enzyme inhibitory protein

COX

Cyclooxygenase

DC

Dendritic cell

ERK

Extracellular signal regulated kinase

FADD

Fas-associated death domain

FasL

Fas ligand

IAP

Inhibitor of apoptosis protein

IL

Interleukin

PG

Prostaglandin

SLE

Systemic lupus erythematosus

TCR

T cell receptor

Th

T helper

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Departments of Medicine and Microbiology-Immunology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA