CD4+ Th1 and CD8+ type 1 cytotoxic T cells both play a crucial role in the full development of contact hypersensitivity

J Immunol. 2000 Dec 15;165(12):6783-90. doi: 10.4049/jimmunol.165.12.6783.

Abstract

The role of CD4(+) vs CD8(+) T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4(+) or CD8(+) T cells to directly address this issue. Mice lacking either CD4(+) or CD8(+) T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice. The depression of CHS was more significant in CD8 KO mice than in CD4 KO mice. Furthermore, in vivo depletion of either CD8(+) T cells from CD4 KO mice or CD4(+) T cells from CD8 KO mice virtually abolished CHS responses. Lymph node cells (LNCs) from hapten-sensitized CD4 and CD8 KO mice showed a decreased capacity for transferring CHS. In vitro depletion of either CD4(+) T cells from CD8 KO LNCs or CD8(+) T cells from CD4 KO LNCs resulted in a complete loss of CHS transfer. LNCs from CD4 and CD8 KO mice produced significant amounts of IFN-gamma, indicating that both CD4(+) and CD8(+) T cells are able to secrete IFN-gamma. LNCs from CD8, but not CD4, KO mice were able to produce IL-4 and IL-10, suggesting that IL-4 and IL-10 are mainly derived from CD4(+) T cells. Intracellular cytokine staining of LNCs confirmed that IFN-gamma-positive cells consisted of CD4(+) (Th1) and CD8(+) (type 1 cytotoxic T) T cells, whereas IL-10-positive cells were exclusively CD4(+) (Th2) T cells. Collectively, these results suggest that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T cells are crucial effector cells in CHS responses to dinitrofluorobenzene and oxazolone in C57BL/6 mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adoptive Transfer
  • Animals
  • CD4 Antigens / biosynthesis*
  • CD4 Antigens / genetics
  • CD8 Antigens / biosynthesis*
  • CD8 Antigens / genetics
  • Dermatitis, Contact / etiology
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / prevention & control
  • Dinitrofluorobenzene / administration & dosage
  • Dinitrofluorobenzene / immunology
  • Immune Sera / pharmacology
  • Immune Tolerance / genetics
  • Injections, Intravenous
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / metabolism
  • Lymph Nodes / transplantation
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxazolone / administration & dosage
  • Oxazolone / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Immune Sera
  • Interleukin-10
  • Oxazolone
  • Interleukin-4
  • Interferon-gamma
  • Dinitrofluorobenzene