The nature of antigen in the eye has a profound effect on the cytokine milieu and resultant immune response

Thomas J. D'Orazio, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The eye is endowed with a number of mechanisms that protect it from immune-mediated injury. One such mechanism, termed anterior chamber-associated immune deviation (ACAID), evokes the antigen-specific, systemic down-regulation of Th1 responses to antigen inoculated into the anterior chamber of the eye. ACAID has been correlated with the selective production of IL-10 by the antigen-presenting cells (APC) and the development of a cross-regulatory Th2-like response. A small subset of antigens do not induce ACAID, but instead provoke IL-12 and normal Th1 immunity. Remarkably, all soluble antigens tested are capable of inducing ACAID; only cell-associated antigens do not induce ACAID. We hypothesized that the nature of antigen plays a decisive role in the resultant immune response. This hypothesis was tested with two well-characterized antigens, ovalbumin (OVA) and SV40 large T antigen (SV40 Lg T Ag). The soluble forms of OVA and SV40 Lg T Ag induced ACAID in both in vivo and in vitro models of the eye. In contrast, the particulate forms of these antigens, i.e. OVA passively absorbed onto inert latex beads (OVA-latex) and SV40 Lg T Ag expressed in two different cell lines, 99E1 and SV-T2, did not induce ACAID in either in vivo or in vitro models of the eye. In addition, the cytokine profiles of ocular APC pulsed with OVA or OVA-latex showed that soluble OVA induced the production of IL-10, whereas OVA-latex induced the production of IL-12. These data suggest that the nature of the antigen in the eye, whether soluble or particulate, is a crucial determinant in the resultant immune response. Moreover, they suggest a mechanism in which soluble antigens preferentially induce the release of ACAID-inducing IL-10 whereas particulate antigens preferentially induce the release of Th1-inducing IL-12 by responding APC.

Original languageEnglish (US)
Pages (from-to)1544-1553
Number of pages10
JournalEuropean Journal of Immunology
Volume28
Issue number5
DOIs
StatePublished - May 1998

Fingerprint

Anterior Chamber
Ovalbumin
Cytokines
Antigens
Latex
Antigen-Presenting Cells
Interleukin-12
Interleukin-10
Polyomavirus Transforming Antigens
Viral Tumor Antigens
Microspheres
Immunity
Down-Regulation
Cell Line
Wounds and Injuries

Keywords

  • Cytokine
  • Macrophage
  • Monocyte
  • Rodent
  • Suppression
  • Th1/Th2
  • Tolerance

ASJC Scopus subject areas

  • Immunology

Cite this

The nature of antigen in the eye has a profound effect on the cytokine milieu and resultant immune response. / D'Orazio, Thomas J.; Niederkorn, Jerry Y.

In: European Journal of Immunology, Vol. 28, No. 5, 05.1998, p. 1544-1553.

Research output: Contribution to journalArticle

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