T cell populations primed by hapten sensitization in contact sensitivity are distinguished by polarized patterns of cytokine production: interferon gamma-producing (Tc1) effector CD8+ T cells and interleukin (Il) 4/Il-10-producing (Th2) negative regulatory CD4+ T cells.
Open Access
- 1 March 1996
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 183 (3), 1001-1012
- https://doi.org/10.1084/jem.183.3.1001
Abstract
Contact hypersensitivity (CHS) is a T cell-mediated response to hapten sensitization of the epidermis. The roles of CD4+ and CD8+ T cells in CHS have remained unclear, however, as studies to define either subset as the T cells mediating CHS have provided conflicting results. The goal of this study was to correlate the in vivo function of CD4+ and CD8+ T cells in CHS with the cytokines produced by each T cell population. Antibody-mediated depletion of CD4+ T cells before sensitization of BALB/c mice with 2,4-dinitrofluorobenzene (DNFB) or oxazolone (Ox) resulted in increased and prolonged CHS responses, indicating CD4+ T cells as negative regulators of the response. Depletion of CD8+ T cells resulted in low or abrogated responses, indicating CD8+ T cells as the effector cells in CHS. Sensitization with DNFB or Ox induced lymph node cell populations of CD8+ T cells producing interferon (IFN)-gamma and no interleukin (Il) 4 or Il-10, and CD4+ T cells producing Il-4 and Il-10 and no or little detectable IFN-gamma. The polarized patterns of cytokine production were stimulated by culture of hapten-primed lymph node cells either on anti-T cell receptor antibody-coated wells or with semipurified Langerhans cells isolated from hapten-sensitized mice. Stimulation of cytokine production during culture of hapten-primed CD4+ or CD8+ T cells with Langerhans cells was hapten specific and restricted to class II or class I major histocompatibility complex, respectively. The induction of the CD4+ and CD8+ T cells producing the polarized patterns of cytokines was not restricted to BALB/c mice, as cells from Ox sensitized C57B1/6 and B10.D2 mice produced the same patterns. Collectively, these results expose the induction of two polarized and functionally opposing populations of T cells by hapten sensitization to induce CHS: IFN-gamma-producing effector CD8+ T cells and Il-4/Il-10-producing CD4+ T cells that negatively regulate the response.Keywords
This publication has 43 references indexed in Scilit:
- Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses.The Journal of Experimental Medicine, 1995
- Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokinesImmunity, 1995
- Development of T H 1 CD4 + T Cells Through IL-12 Produced by Listeria -Induced MacrophagesScience, 1993
- NK1.1+ CD4+ CD8‐ thymocytes with specific lymphokine secretionEuropean Journal of Immunology, 1993
- Early molecular events in the induction phase of contact sensitivity.Proceedings of the National Academy of Sciences, 1992
- Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions.The Journal of Experimental Medicine, 1991
- TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional PropertiesAnnual Review of Immunology, 1989
- Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.The Journal of Experimental Medicine, 1989
- A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma.The Journal of Immunology, 1986
- ELICITATION OF DELAYED ALLERGIC SKIN REACTIONS WITH HAPTENS: THE DEPENDENCE OF ELICITATION ON HAPTEN COMBINATION WITH PROTEINThe Journal of Experimental Medicine, 1952