Distinct regulation of HLA class II and class I cell surface expression in the THP-1 macrophage cell line after bacterial phagocytosis

Andrea De Lerma Barbaro, Giovanna Tosi, Maria Teresa Valle, Anna Maria Megiovanni, Silvia Sartoris, Antonella D'Agostino, Ornella Soro, Maria Cristina Mingari, G. Walter Canonica, Fabrizio Manca, Roberto S. Accolla

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of HLA and CD1b molecules was investigated in the THP-1 macrophage cell line within 2 weeks following phagocytosis of mycobacteria or Escherichia coli. During the first 2-3 days, cell surface expression of HLA class II and CD1b was drastically down-modulated, whereas HLA class I expression was up-modulated. In the following days both HLA class II and CD1b expression first returned to normal, then increased and finally returned to normal with kinetics similar to that observed for the steadily increased HLA class I. The initial down-modulation of HLA class II and CD1b cell surface antigens was absolutely dependent on phagocytosis of bacteria. Further studies indicated that initial HLA class II cell surface down-modulation (1) was not due to reduced transcription or biosynthesis of mature HLA class II heterodimers, (2) was only partially, if at all, rescued by treatment with IFN-γ although both mRNA and corresponding intracellular proteins increased up to sixfold with respect to untreated cells, and (3) resulted in failure of THP-1 cells to process and present mycobacterial antigens to HLA-DR-restricted antigen-specific T cell lines. The existence of a transient block of transport of mature HLA class II heterodimers to the cell surface in the first days after phagocytosis of bacteria may have negative and positive consequences: it decreases APC function early but it may increase it later by favoring optimal loading of bacterial antigens in cellular compartments at high concentration of antigen-presenting molecules.

Original languageEnglish
Pages (from-to)499-511
Number of pages13
JournalEuropean Journal of Immunology
Volume29
Issue number2
DOIs
Publication statusPublished - 1999

Keywords

  • Bacterium
  • CD1b
  • HLA expression
  • IFN-γ
  • Phagocytosis

ASJC Scopus subject areas

  • Immunology

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