CD8+ T cell migration to the skin requires CD4+ help in a murine model of contact hypersensitivity

PLoS One. 2012;7(8):e41038. doi: 10.1371/journal.pone.0041038. Epub 2012 Aug 20.

Abstract

The relative roles of CD4+ and CD8+ T cells in contact hypersensitivity responses have not been fully solved, and remain an important question. Using an adoptive transfer model, we investigated the role of the respective T cell subset. Magnetic bead separated CD4+ and CD8+ T cells from oxazolone sensitized C57BL/6 mice were transferred into RAG-/- mice, followed by hapten challenge and analysis of inflammatory parameters at 24 hours post exposure. The CD4+ T cell recipient mice developed partial contact hypersensitivity responses to oxazolone. CD8+ T cells caused significant amplification of the response in recipients of both CD4+ and CD8+ T cells including ear swelling, type 1 inflammatory mediators, and cell killing. Unexpectedly, CD8+ T cells were not sufficient to mediate contact hypersensitivity, although abundantly present in the lymph nodes in the CD8+ T cell reconstituted mice. There were no signs of inflammation at the site of hapten exposure, indicating impaired recruitment of CD8+ T cells in the absence of CD4+ T cells. These data show that CD4+ T cells mediate contact hypersensitivity to oxazolone, but CD8+ T cells contribute with the most potent effector mechanisms. Moreover, our results suggest that CD4+ T cell function is required for the mobilization of CD8+ effector T cells to the site of hapten exposure. The results shed new light on the relative importance of CD4+ and CD8+ T cells during the effector phase of contact hypersensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement*
  • Dermatitis, Contact / immunology*
  • Disease Models, Animal*
  • Flow Cytometry
  • Mice
  • Paraffin Embedding

Grants and funding

This work was partly supported by grants from the Academy of Finland (Contracts No 213072 and 214479). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.