Short communication Relationships between natural T cells, atopy, IgE levels, and IL-4 production Background: Th2 cells govern allergic disorders. Mechanisms leading to the Th2 commitment are dominated by the requirement of IL-4. A potential source of this triggering IL-4 could be the CD4+ subset of a small population of T cells, natural T (NT) cells. Indeed, this subset is involved in IgE responses in mice and produces promptly high amounts of IL-4 in both mice and man. Methods: NT cells were identi®ed in peripheral blood by ¯ow cytometry with antibodies against Va24 and Vb11, recognizing the T-cell receptor speci®c for NT cells. Simultaneous staining with anti-CD3, anti-CD4, or anti-CD8 antibodies was performed. The frequency of NT cells in man was studied according to the presence of atopy de®ned by the positivity of skin tests, according to total IgE levels in serum, and according to IL-4 concentration of whole-blood culture supernatants determined by a ¯ow cytometer microsphere- based assay. Results: Seventy subjects were included, of whom 30 were atopic. The number of CD4+ NT cells was higher in atopics than in nonatopics (P=0.009). This number was correlated to the total IgE levels (r=0.34, P=0.03). In addition, the number of CD4+ NT cells, but also of CD8+ NT cells, was correlated to the levels of IL-4 (r=0.71, P=0.01, and r=0.6, P=0.03, respectively). Conclusions: These results show that the number of NT cells, particularly the CD4+ subset, is related to atopy, IL-4 production, and IgE levels. Therefore, this population of T cells is likely to play a role in the Th2 commitment initiating atopic diseases. A. Magnan, L. Me Âly, S. Prato, D. Vervloet UPRES 2050, Groupe de Recherche Clinique ``Pathologie respiratoire et cutane Âe lie Âe a Á l'environnement'', Service de Pneumo-Allergologie, et Centre d'Investigations Cliniques, INSERM, Assistance Publique Ho Ãpitaux de Marseille, Hopital Ste Marguerite, Marseilles F. Romagne Â, C. Camilla, A. Necker, B. Casano, F. Montero-Jullian, V. Fert Immunotech, BP 177, Marseilles B. Malissen Centre d'immunologie INSERM-CNRS de Marseille- Luminy, Marseilles P. Bongrand INSERM U 387, Hopital Ste Marguerite, Marseilles, France Key words: allergy; atopy; IgE; IL-4; NT cells; T cells; Th2. Dr A. Magnan Service de Pneumo-Allergologie Hopital Ste-Marguerite 270 Bd de Ste Marguerite 13274 Marseille Cedex 09 France Accepted for publication 16 November 1999 Many data suggest that atopic diseases are orchestrated by Th2 cells, which mainly produce interleukin (IL)-4, IL-5 (but no or little IL-2), and interferon (IFN)-c (1). Therefore, a major objective of allergy research is the elucidation of the mechanisms underlying the Th2 commitment. Among these mechanisms, IL-4 itself is a major agent (2). However, the cells producing the IL-4 required for the development of Th2 cells are unknown (3, 4). A small population of special T cells, called natural T (NT) cells because of characteristics shared with natural killer (NK) cells, was recently identi®ed in mice (5, 6) and man (7). In mice, NT cells express the NK 1.1 antigen and account for 1% of lymph-node and 2% of mature spleen T cells. They all express an invariant T-cell receptor (TCR) alpha chain. Human NT cells express the NK-speci®c CD56 antigen and an invariant TCR composed of a Va24JaQ chain paired with Vb11 (8, 9). The cognate ligand of the NT cell receptor was shown to be CD1 in mice, a major histocompatibility class-I-related antigen (5, 6), and it is CD1d in man (10). Some murine NT cells express CD4, but not CD8. By contrast, the human counterpart can express CD4 or CD8. However, when expressed on human NT cells, CD8 is in the homodimeric form CD8aa, and the CD8b chain is not detected (8, 9). This phenotype is reminiscent of cd T cells, another reactive T-cell population, and of NK cells. Together with the expression on these cells of the IL-2 receptor beta chain and CD44, the expression of CD8aa suggests a state of Allergy 2000: 55: 286±290 Printed in UK. All rights reserved Copyright # Munksgaard 2000 ALLERGY ISSN 0105-4538 286