The quantitative and qualitative defect of CD4⁺ CD45RO⁺ memory‐type T cells are involved in the abnormality of TH1 immunity in atopic dermatitis patients

Abstract

Peripheral blood mononuclear cells (PBMCs) obtained from atopic dermatitis (AD) patients produced low levels of IFN-gamma in response to Dermatophagoides farinae antigen (Der f Ag) plus IL-2 or OKT3 MoAb in contrast with PBMCs obtained from healthy donors. The reduced IFN-gamma production in AD patients' T cells appeared to be derived from the defect of CD4+ T cells but not CD8+ T cells. Indeed, from the cytoplasmic staining analysis of cytokines, it was demonstrated that the frequency of IFN-gamma producing CD4+ T cells (TH1 cells) in AD patients was markedly lower than that of healthy donors. From the phenotypic analysis using flow cytometry, it was also found that the number of CD4+ CD45RO+ memory type T cells was significantly reduced in AD patients compared with that of healthy donors. In addition to quantitative defect of memory type CD4+ T cells, functional defect of CD4+ CD45RO+ memory type T cells was also demonstrated in AD patients. Enriched CD4+ CD45RO+ T cells obtained from AD patients, who exhibited greatly reduced delayed-type hypersensitivity (DTH) response in tuberculin test, showed no significant TH1 immunity in terms of IFN-gamma production by stimulation with OKT3 MoAb or purified protein derivative (PPD). Thus, the immunological abnormality of TH1 immunity in AD patients appeared to be induced in concomitant with both the quantitative and qualitative defect of memory type CD4+ T cells.

Prominent Involvement of Activated Th1-Subset of T-Cells and Increased Expression of Receptor for IFN-Gamma on Keratinocytes in Atopic Dermatitis Acute Skin Lesions

“…It has also been noted that immunological abnormality of Th1 immunity in AD patients is induced concomitantly with both the quantitative, qualitative and functional defect of memory type CD4+ T-cells, as supported by significantly reduced number of CD4+ CD45RO+ memory type T-cells found on PBMC of AD patients [26]. …”

Generation of CD4+CD45RA+ Effector T Cells by Stimulation in the Presence of Cyclic Adenosine 5′-Monophosphate- Elevating Agents

“…In atopic patients a quantitative and qualitative defect in CD4 ϩ CD45RO ϩ T cells has been reported, whereas CD4 ϩ CD45RA ϩ T lymphocytes secreted IL-4 and IL-5 and could promote IgE and IgA production. The frequency of cells responding to allergens within the CD45RA subset was 7-to 20-fold higher than that in nonatopic patients (44,45). Activated CD4 ϩ CD45RA ϩ T lymphocytes were also the prevailing inflammatory cell population in discoid lupus and children with nephrotic syndrome (46 -48).…”

Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5

“…AD is considered to be a Th2-mediated disease with high serum IgE involvement. 5 Peripheral blood mononuclear cells from patients with AD have increased capacity to produce IL-4, IL-5 and IL-13 but limited capacity to produce interferon (IFN)-c. [6][7][8] The effects of Th2 cytokines are counteracted by Th1 cytokines, which include IFN-c and IL-12. Under normal immune conditions, there is a balance between Th1 and Th2 cytokines.…”