In-vivo impaired T helper 1 cell development in submandibular lymph nodes due to IL-12 deficiency following antigen injection into the anterior chamber of the eye

Victor L. Perez, Andre Biuckians, J. Wayne Streilein

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Purpose: To determine the functional properties of antigen-specific T cells that accumulate in lymph nodes following injection of antigen into the anterior chamber (AC). Methods: Ovalbumin (OVA) specific, CD4+ transgenic T cell receptor (Tcr) T cells (KJ-126+) from DO11.10 mice were adoptively transferred into unirradiated syngeneic BALB/c mice who then received an injection of OVA in the AC or subcutaneously (SC). Three days later, KJ126+ T cells in draining and non-draining lymph nodes were analyzed for clonal expansion, activation, and cell-cycle status by flow cytometry. In addition, the cells' functional phenotype was assessed in vitro by proliferation assays and cytokine production by ELISA. Results: Tcr T cells localized exclusively to draining lymph nodes after injection of OVA into the AC (neck) and SC (neck, axilla, brachial). In both cases, the KJ126+ T cells displayed evidence of in-vivo activation and proliferation. T cells from AC-injected donors when stimulated in vitro with OVA produced small amounts of IL-2, but no IFN-γ, IL-4, IL-5, IL-10, or TGFβ. By contrast, T cells from SC-injected animals displayed a Th1-like phenotype (IL-2, IFN-γ). The draining lymph nodes of mice that received systemic or intraocular administration of exogenous IL-12 at the time of the AC injection of OVA also contained KJ126+ T cells that secreted IFN-γ and IL-2. Conclusion: Antigen attracts antigen-specific T cells to lymph nodes that drain the injection site. Whereas responding T cells in nodes draining SC-injection sites differentiated into Th1-like cells, T cells in nodes draining AC injection failed to differentiated beyond the capacity to secrete IL-2 in response to antigen. Since the failure was reversed by exogenous IL-12, we propose that orderly differentiation of antigen-specific T cells down the Th1 pathway is aborted by the eye, because of a deficit in IL-12 production.

Original languageEnglish (US)
Pages (from-to)9-24
Number of pages16
JournalOcular Immunology and Inflammation
Volume8
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Antigen presentation
  • Cytokines
  • In-vivo animal model
  • Lymph node
  • Th1/Th2

ASJC Scopus subject areas

  • Ophthalmology
  • Immunology and Allergy

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