Initial Recruitment of Interferon‐γ‐Producing CD8+ Effector Cells, Followed by Infiltration of CD4+ Cells in 2,4,6‐Trinitro‐1‐Chlorobenzene (TNCB)‐Induced Murine Contact Hypersensitivity Reactions

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Abstract
Contact hypersensitivity (CHS) is an antigen-specific, T-cell-mediated skin reaction in sensitized individuals. Recent studies have demonstrated that the murine CHS reaction to 2,4-dinitrofluorobenzene (DNCB) is mediated by CD8+ T cells and down-regulated by CD4+ T cells. We studied cellular events and functions of infiltrating cells in CHS reactions to 2,4,6-trinitro-1-chlorobenzene (TNCB) in the skin and draining lymph nodes (LN) of BALB/c mice and compared them with the CHS reaction to a house dust mite antigen, Dermatophagoides farinae (Df). Mice were sensitized with TNCB or Df antigens, and CHS reactions elicited with the corresponding antigens were examined immunohistologically. Cytokines produced by individual cells isolated from the CHS reactions were analyzed by flow cytometry, and the expression of cytokine mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR). Results demonstrated that the intensity of TNCB-elicited CHS skin reactions reached its peak at 24 hr after elicitation and decreased gradually. Flow cytometric analysis of isolated cells from the TNCB-elicited CHS reactions demonstrated that the infiltrating cells were composed of approximately 25% CD4+ and CD8+ cells at 12, 24, and 36 hr after challenge, although infiltrating cells became dense at 36 hr by histological observation. The percentage of IFN-gamma-producing CD8+ cells (Tc1) in the cell fractions reached its peak at 12 hr and decreased gradually. The peak infiltration of IFN-gamma-producing CD4+ cells (Th 1) was observed at 24 hr. IL-4-producing cells, however, were always below 5% in the cell fractions. The RT-PCR method demonstrated that IFN-gamma mRNA was detected in the TNCB-elicited skin reactions at 12, 18 and 24 hr after elicitation, became weak at 48 hr, and disappeared at 72 hr. No IL-4 mRNA was detected from 12 to 72 hr. In the draining LN cells, however, the percentages of both IFN-gamma-producing CD8+ (Tc1) and CD4+ cells (Th1) decreased 12 to 36 hr after TNCB elicitation. CHS reactions of Df antigens were predominantly composed of infiltrations of CD4+ cells in to the skin, associated with the expression of IL-4 mRNA from 12 to 48 hr after elicitaion. The expression of IFN-gamma mRNA was detected at 48 hr or later. Our findings indicate that the CHS skin reaction to TNCB is induced by early recruitment of IFN-gamma-producing CD8+ effector cells (Tcl), followed by infiltration of IFN-gamma-producing CD4+ cells (Th1), whereas IL-4-producing T cells (Th2) induce the early CHS response to Df antigens.

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