Roles of CD4+ and CD8+ T cells in murine contact sensitivity revealed by in vivo monoclonal antibody depletion.

Abstract

mAb specific for murine CD4+ and CD8+ T cell subsets were utilized to determine the populations participating in delayed-in-time, cutaneous hypersensitivity responses in BALB/c mice. In vivo depletions of these T cell phenotypes revealed that delayed-type hypersensitivity to cellular and protein Ag were mediated by CD4+ effector cells, whereas CD8+ cells down-regulated such responses. Similar depletions in mice prior to sensitization with the hapten 1-fluoro-2,4-dinitrobenzene demonstrated a more complex pattern of cell participation in contact sensitivity (CS) responses. Depletion of CD4+ cells resulted in strikingly enhanced ear swelling, indicating not only an important effector role for CD8+ cells but also a down-regulatory role for some CD4+ cells; depletion of CD8+ cells revealed that some CD4+ cells also act as CS effectors. In vitro depletion of immune lymph node cells with the same mAb before adoptive transfer confirmed CS effector roles for both subsets, and also suggested that at least some CD4+ suppressors act on the efferent limb of the CS response, perhaps by down-regulating the activity of CD8+ effector cells. Partial in vivo depletion with small amounts anti-CD4 mAb and subsequent flow cytometric analysis of residual CD4+ cells was consistent with the hypothesis that CD4+ CS effector cells express a higher density of the CD4 antigen than do CD4+ suppressor cells, raising the possibility that these two functionally distinct CD4+ populations might be separable on the basis of their surface expression of CD4.

CD8+ tissue‐resident memory T cells recruit neutrophils that are essential for flare‐ups in contact dermatitis

“…16,[29][30][31][32][33][34] In the acute CHS assay, the inflammatory response as measured as changes in ear thickness peaks 24 h after the challenge. 35,36 In contrast, in our model, the challenge response seen in allergen-naïve skin peaked 72 h after the challenge in accordance with a classical delayed type IV allergic reaction mediated by memory T cells, and in line with the optimal time for reading patch test responses in the clinic. 17 Importantly, whereas our model allows time for the development of allergen-specific memory T cells, including epidermal CD8 + T RM cells, the acute CHS assay where sensitization and challenge are separated by only 5-7 days does not allow for the development of memory T cells.…”

“…Up to now, the vast majority of these studies have used the acute CHS assay, where mice are sensitized on the abdomen or flank once or twice and then challenged on allergen‐naïve skin on the ears only 5–7 days after the sensitization 16,29‐34 . In the acute CHS assay, the inflammatory response as measured as changes in ear thickness peaks 24 h after the challenge 35,36 . In contrast, in our model, the challenge response seen in allergen‐naïve skin peaked 72 h after the challenge in accordance with a classical delayed type IV allergic reaction mediated by memory T cells, and in line with the optimal time for reading patch test responses in the clinic 17 .…”

CD4+ T cells inhibit the generation of CD8+ epidermal‐resident memory T cells directed against clinically relevant contact allergens

“…In this study, we show that the clinically relevant contact allergens cinnamal, PPD and MI induce a strong CD4 + T cell‐mediated anti‐inflammatory response that impairs the generation of pathogenic epidermal CD8 + T RM cells. In accordance, previous studies using the short CHS model have pointed towards an anti‐inflammatory role of CD4 + T cells in ACD 14,17–25 . However, this is the first study to demonstrate that CD4 + T cells can inhibit the generation of pathogenic epidermal CD8 + T RM cells.…”

“…To determine whether CD4 + T cells might play an inhibitory role in the responses to cinnamal, PPD and MI as previously indicated for fragrance allergens, 14 we CD4 + T cells in ACD. 14,[17][18][19][20][21][22][23][24][25] However, this is the first study to demonstrate that CD4 + T cells can inhibit the generation of pathogenic epidermal CD8 + T RM cells.…”

Anti-Inflammatory and Antipruritic Effects of Remote Ischaemic Postconditioning in a Mouse Model of Experimental Allergic Contact Dermatitis

“…T-cells, which are activated in response to the allergen during the sensitisation period, rapidly release their specific cytokines upon re-exposure to the allergen. Activated CD8 + T cells (Tc) generally have a pro-inflammatory effect, whereas CD4 + T cells (Th) can have a pro-or anti-inflammatory effect; that is, they have a regulatory function [4,5]. The effects of Tc and Th cell subtypes are the subject of research [6,7].…”