Ig gene-like molecule CD31 plays a nonredundant role in the regulation of T-cell immunity and tolerance.
CD31 is an Ig-like molecule expressed by leukocytes and endothelial cells with an established role in the regulation of leukocyte trafficking. Despite genetic deletion of CD31 being associated with exacerbation of T cell-mediated autoimmunity, the contribution of this molecule to T-cell responses is largely unknown. Here we report that tumor and allograft rejection are significantly enhanced in CD31-deficient mice, which are also resistant to tolerance induction. We propose that these effects are dependent on an as yet unrecognized role for CD31-mediated homophilic interactions between T cells and antigen-presenting cells (APCs) during priming. We show that loss of CD31 interactions leads to enhanced primary clonal expansion, increased killing capacity, and diminished regulatory functions by T cells. Immunomodulation by CD31 signals correlates with a partial inhibition of proximal T-cell receptor (TCR) signaling, specifically Zap-70 phosphorylation. However, CD31-deficient mice do not develop autoimmunity due to increased T-cell death following activation, and we show that CD31 triggering induces Erk-mediated prosurvival activity in T cells either in conjunction with TCR signaling or autonomously. We conclude that CD31 functions as a nonredundant comodulator of T-cell responses, which specializes in sizing the ensuing immune response by setting the threshold for T-cell activation and tolerance, while preventing memory T-cell death.
Ma
Liang
L
Section of Immunobiology and Inflammation and Signal Transduction, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom.
Mauro
Claudio
C
Cornish
Georgina H
GH
Chai
Jian-Guo
JG
Coe
David
D
Fu
Hongmei
H
Patton
Daniel
D
Okkenhaug
Klaus
K
Franzoso
Guido
G
Dyson
Julian
J
Nourshargh
Sussan
S
Marelli-Berg
Federica M
FM
D000818:Animals; D002470:Cell Survival; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005803:Genes, Immunoglobulin; D007108:Immune Tolerance; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D019408:Platelet Endothelial Cell Adhesion Molecule-1