Cytokine-induced expression of CD1b molecules by peripheral blood monocytes: influence of 3'-azido-3'-deoxythymidine.
CD1b is a nonpolymorphic, MHC-like molecule, capable of presenting non-peptide antigens (Ags) to CD3+, CD4-, CD8-, alphabeta or gammadelta T lymphocytes. Previous studies have shown that CD1b can be induced in monocytes/macrophages by GM-CSF+IL-4, and can restrict their presentation of Mycobacterium tuberculosis antigen (Ag) to Ag-specific T cells. Since a number of HIV-positive subjects undergo mycobacterial infections, preliminary studies have been performed to explore whether anti-HIV chemotherapy would influence cytokine-induced CD1b expression in peripheral blood monocytes. The results obtained by treating monocytes with GM-CSF+IL-4, in presence or absence of 3'-azido-3'-deoxythymidine (AZT) showed that: (a) the majority of adherent mononuclear cells (AMNC) collected from peripheral blood of healthy donors, express CD1b molecule on the cell membrane, upon treatment with GM-CSF+IL-4; (b) CD1b appearance is mainly due to the de novo induction of CD1b gene expression (as confirmed by Northern blot analysis), rather than to migration of the molecule from the cytoplasm to the plasma membrane (as suggested by Western blot analysis); (c) AZT does not alter the percentage of CD1b+ AMNC treated with the cytokines; (d) however, AZT inhibits cytokine-induced proliferation of AMNC, thus reducing the overall Ag-presenting potential of the host. Our results suggest that the anti-proliferative effect of AZT could depress anti-mycobacteria immunity in AZT-treated subjects, which may have important implication for the clinical outcome of patients harbouring inadequately treated mycobacterial infections.
Giuliani
A
A
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Tentori
L
L
Pepponi
R
R
Porcelli
S A
SA
Aquino
A
A
Orlando
L
L
Sugita
M
M
Brenner
M B
MB
Bonmassar
E
E
Graziani
G
G
D019380:Anti-HIV Agents / Q000494:pharmacology*; D018949:Antigens, CD1 / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D013268:Stimulation, Chemical; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D018949:Antigens, CD1; D015847:Interleukin-4; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor