Decreased accessory cell function and costimulatory activity by 1,25-dihydroxyvitamin D3-treated monocytes.
To characterize the mechanism(s) by which 1,25-dihydroxyvitamin D3 (calcitriol) modulates the costimulatory capacity of monocytes, we examined the effect of calcitriol pretreatment of monocytes on their capacity to promote T cell proliferation (accessory cell function). Correlation of calcitriol-dependent changes in monocyte accessory cell function and alterations in phenotype and cytokine production, and the dependence of these changes on cell viability, were studied. Calcitriol pretreatment induced a defect in accessory cell function that was evident with fixed monocytes, suggesting a cell-surface-associated mechanism. Altered accessory cell function did not correlate with changes in HLA-DR antigen expression and was unaffected by concurrent treatment with interferon-gamma. Calcitriol treatment did not alter either the expression of adhesion molecules or monocytic production of interleukin-1 beta (IL-1 beta) or IL-6. Exogenous IL-1 or IL-6 did not overcome the impaired costimulatory activity of calcitriol-treated monocytes. Thus, calcitriol treatment reduces the capacity of monocytes to promote lectin-induced T cell activation at the level of the plasma membrane, perhaps through altered expression of an uncharacterized molecule important in monocyte-T cell interactions. At chronically inflamed sites, elaboration of calcitriol by activated macrophages may regulate the ability of monocytes to induce both antigen-dependent and antigen-independent T cell proliferation.
Department of Microbiology, Dartmouth-Hitchcock Medical Center, Hanover, NH.
W F
WF
Rigby
M G
MG
Waugh
D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000502:physiology; D015703:Antigens, CD / Q000502:physiology; D018968:CD58 Antigens; D002117:Calcitriol / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037102:Lectins / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D015703:Antigens, CD; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D037102:Lectins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D002117:Calcitriol