Journal of Immunology Research

Review Article

Exogenous Control of the Expression of Group I CD1 Molecules Competent for Presentation of Microbial Nonpeptide Antigens to Human T Lymphocytes

Table 4

Effect of biological or physical agents on CD1 molecule expression.


Type of biological agents	Agent	CD1^a	ED^b	Ref.^c	Observations

Growth factors	Placental growth factor (PLGF)	U	ED-2	[201]	Modest upregulation. PLGF antagonizes LPS-induced down-regulation of CD1a in iDCs. Mechanism: inhibition of NF-kB signal transduction pathway.

Heat-shock proteins	HSP-27	D	ED-1	[202, 203]	Mechanism: IL-10 induction.

Immuno-complexes	Anti-OVA rabbit IgG + OVA	D	ED-1	[204]	Mechanism: interaction with FcγRI and FcγRII.

Ligand proteins	Peptide ligand of melanocortin-4 receptor (NDP-MSH)	D	ED-4	[205]	mDCs from treated precursors show impaired ability to prime T-cells.
Ligand proteins	sLAG-3 (CD223) soluble MHC-II ligand	D	ED-1 ED-3	[206]	CD1a down-regulation. Mechanism (hypothesis): phosphorylation of PLCγ2, p72syk, or AKT molecules.

Lipids	Lipids	D	ED-1	[207]	High individual variability of CD1a induction after G4. Lipoproteins (VLDL > LDL > HDL) and PPARγ activation reduce the number of G4-induced CD1a⁺ cells.
	Lysophosphatidic acid (LPA)	D	ED-1	[208]	Mechanism: LPA is a potent natural ligand for PPARγ.
	Oxidized Phospholipids	D	ED-1	[209]	Oxidized phospholipids (generated during inflammation) down-regulate CD1a/b/c and block histone modifications required to activate mDCs.

Malignant cell products	Hepatoma cell supernatant	D	ED-1	[210]	CD1a down-regulation by hepatoma but not normal liver cell supernatants. Induction of Treg Mechanism: possibly IL-10-dependent.
	Human renal cell carcinoma lines	D	OED	[211]	From CD34⁺ progenitor cells: severe inhibition of CD1a and APC function of induced CDs. Mechanism: possibly due, at least in part, to IL-6 and macrophage colony stimulating factor.
	Leukemia cell supernatant	D	ED-1	[212]	Supernatant of K562, HL-60 and DAUDI on CD1a expression. Mechanism: at least in part, due to IL-1β secreted by MOs in response to leukemic cell products.
	Melanoma cell supernatant	D	ED-1 IvDC	[213]	CD1a/b/c. Mechanism: IL-10 release induction in vivo reduced CD1-positive cells in metastatic melanoma.
		D	OED	[214]	LC generated in vitro from cord blood CD34⁺ progenitors are CD1a-deficient when cultured with melanoma cells in a transwell design setting.
	Supernatant from primary or long-term cultured tumor cells	D	ED-1	[215]	Reduction of CD1a by supernatant of tumor cell lines was much less active respect to supernatants of primary tumors. Similar results obtained with CD34⁺ progenitor-derived DCs. Mechanism: at least in part mediated by PGE2 released by primary tumor cells.

Nucleotides	cAMP, cGMP	D	ED-1	[216]	cAMP increase was mimicked by the adenylate cyclase activator forskolin or cAMP analog 8 bromo-cAMP; cGMP increase was mimicked by 8 bromo-cGMP; increase of both was induced by PDE inhibitor IBMX. Down regolation of CD1a is followed by impairment of LPS-induced mDC function.

Serum and serum components	Human serum	D	ED-1	[217]	Human serum lipids: impairment of CD1a/b/c transcription. Reduced induction of CD1c-restricted T-cell responses. Mechanism: PPARγ activation.
				[218]	Human serum: Mechanism: PPARγ activation and IL-10 induction.
				[219]	Autologous serum (iDCs from MOs or from CD34⁺ precursors).
	IgG	D	ED-1	[220]	Down-regulation of CD1a/b/c and upregulation of CD-1d transcripts. Mechanism: IgG-mediated activation of Fcγ receptor FcγRIIa (CD32a).
		D	ED-1 ED-4	[221]	This study starts from the observation that intravenous immunoglobulin attenuates MS.
	β2-microblobulin	D	ED-1 ED-4	[222]	Down-regulation of CD1a and mDC function. Mechanism: inhibition of MAPK, ERK, MEK, and NF-kB, and activation of STAT3.

Physical agents

Ultraviolet light	UVAI (340–400 nm)	D	IvDC	[223]	Decrease of CD1a⁺ LC in a epidermis 3 days after ultraviolet exposure.
	UVB	D	IvDC	[224]	UV irradiation induces CD1a⁺ LC down-regulation and IL-10 induction in vivo in skin. This is prevented in vivo by Zn-containing or octylmetoxy cinnamate sunscreen preparations.
		D	IvDC	[225]	CD1a⁺ Langerhans cell loss after exposure of human epidermis and dermis to UVB, accompanied by infiltration with IL-10 producing macrophages.
		D	IvDC	[226]	Organ culture in vitro of human cornea (immunohistochemistry): low-dose UVB (100 mJ/cm²) decreases HLA-DR and CD1a expression of organ-cultured human corneas and induces moderate corneal injuries, and might be useful for preventing allograft rejection.

^aEvaluation of CD1a expression if not otherwise specified: U: upregulation; D: down-regulation.
^bExperimental design code (see Figure 2).
^cReference number.