Dysregulated expression of CD69 and IL‐2 receptor α and β chains on CD8+ T lymphocytes in flaky skin mice

• Published in: Immunology and cell biology Vol. 78; no. 6; pp. 596 - 602
• Main Authors: Abernethy, Nevin J, Hagan, Colin, Tan, Paul LJ, Watson, James D
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-12-2000
• Subjects: Animals; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; CD122; CD25; CD3 Complex - immunology; CD69; CD8-Positive T-Lymphocytes - immunology; Female; Flow Cytometry; interleukin‐2 receptor; Lectins, C-Type; Lymph Nodes - immunology; lymphadenopathy; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; psoriasis; Psoriasis - immunology; Receptors, Interleukin-2 - biosynthesis; T‐cell activation; Up-Regulation
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1046/j.1440-1711.2000.00945.x

T‐cell activation is considered to be an important element in the pathogenesis of psoriasis, a human skin disease characterized by keratinocyte hyperproliferation, altered keratinocyte differentiation and inflammation of the dermis and epidermis. Mice homozygous for the flaky skin (fsn) mutation develop a skin disorder that has histopathological and biochemical features resembling some forms of psoriasis. It has been reported recently that peripheral lymph nodes (PLN) in fsn/fsn mice exhibit various abnormalities in T‐cell development suggestive of dysregulated T‐ and B‐cell activation. In the present study, the expression of the inducible T‐cell activation antigens CD69 and IL‐2 receptor α chain (CD25) on PLN cells from fsn/fsn mice and their phenotypically normal littermates is examined. Expression of CD69 was significantly increased on PLN cells in fsn/fsn mice (mean ± SD, 49.9 ± 14.7% of cells) compared with control mice (14.6 ± 4.2 %). Analysis of CD4+ and CD8+ T cell subsets revealed that expression of CD69 in fsn/fsn PLN was significantly biased toward CD8+ cells. Although expression of CD25 was preferentially associated with CD4+ rather than CD8+ cells in both fsn/fsn and control PLN, with most CD4+CD25+ cells being CD25hi, the proportion of CD4+ cells expressing CD25 was higher in fsn/fsn than control PLN. In contrast, CD25 was expressed by 2–3 % of CD8+ PLN cells in both fsn/fsn and control mice and CD25hi cells accounted for < 1 % of CD8+ cells in fsn/fsn PLN. The paucity of CD25 on CD8+ cells in fsn/fsn PLN did not appear to be due to a defect in the ability of these cells to upregulate CD25, because T cell receptor stimulation in vitro induced high expression of CD25 on both CD4+ and CD8+ cells. A striking and consistent finding was that most CD8+ cells in fsn/fsn PLN expressed high levels of IL‐2R β chain (CD122). In contrast, CD122 was expressed at low levels on CD8+ cells in control mice. Analysis of PLN cells from newborn fsn/fsn mice revealed that the high expression of CD122 on CD8+ cells was established by 2 weeks of age, prior to the appearance of clinical skin disease. These data indicate that large numbers of T cells in fsn/fsn mice are activated and reinforce the view that fsn is an important regulator of lymphocyte development and function. The relationship between T‐cell activation and flaky skin disease in these mice remains to be established.