Human monocytes differentiate into dendritic cells subsets that induce anergic and regulatory T cells in sepsis.
BACKGROUND
Sepsis is a multifactorial pathology with high susceptibility to secondary infections. Innate and adaptive immunity are affected in sepsis, including monocyte deactivation.


RESULTS
To better understand the effects of alterations in monocytes on the regulation of immune responses during sepsis, we analyzed their differentiation in dendritic cell (DC). Cells from septic patients differentiated overwhelmingly into CD1a-negative DC, a population that was only a minor subset in controls and that is so far poorly characterized. Analysis of T cell responses induced with purified CD1a-negative and CD1a+ DC indicated that (i) CD1a-negative DC from both healthy individuals and septic patients fail to induce T cell proliferation, (ii) TGFβ and IL-4 were strongly produced in mixed leukocyte reaction (MLR) with control CD1a-negative DC; reduced levels were produced with patients DC together with a slight induction of IFNγ, (iii) compared to controls, CD1a+ DC derived from septic patients induced 3-fold more Foxp3+ T cells.


CONCLUSIONS
Our results indicate a strong shift in DC populations derived from septic patients' monocytes with expanded cell subsets that induce either T cell anergy or proliferation of T cells with regulatory potential. Lower regulatory cytokines induction on a per cell basis by CD1a-negative dendritic cells from patients points however to a down regulation of immune suppressive abilities in these cells.
INSERM UMRS 940, Paris, France.
Valérie
V
Faivre
Anne Claire
AC
Lukaszewicz
Arnaud
A
Alves
Dominique
D
Charron
Didier
D
Payen
Alain
A
Haziot
D018949:Antigens, CD1 / Q000276:immunology; D002454:Cell Differentiation; D017635:Clonal Anergy; D003713:Dendritic Cells / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology*; D018805:Sepsis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D018949:Antigens, CD1; C419393:CD1a antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors