SUMMARYThe absence of CD7 protein and the corresponding mRNA is a stable feature in a subset of normal circulating CD4 memory T cells. It is still unresolved whether the CD7 ÿ subset represents a specific Tcell lineage. Here we show that repeated stimulation of highly purified CD4 CD45RA CD45RO ÿ naive T cells in vitro leads to the development of a distinct memory subset that is defined by the expression versus non-expression of the CD7 antigen. Comparing different T-cell activation pathways (TCR/CD3, CD2), we observed that alternative signals were critically involved in the development of CD4 + CD7 ÿ T cells. Peak mean numbers of CD7 ÿ memory cells occurred after 3-5 cycles of restimulation in vitro. Naive T cells that had undergone repeated stimulations were harvested and sorted into CD7and CD7 ÿ subsets. The vast majority (> 97%) of CD7 T cells retained their expression, whereas the CD7 ÿ population did not re-express the antigen during further propagation of separated Tcell subsets. In CD7 ÿ cells no CD7 mRNA was monitored, indicating transcriptional regulation of CD7 expression. Certain differentiation-related antigens, including the cutaneous lymphocyte antigen CLA, were preferentially expressed on CD7 ÿ T cells. We suggest that absence of CD7 expression in a subset of CD4 memory cells reflects a separate and stable differentiation state occurring late in the immune response. These T cells may represent the physiological counterpart of malignant T cells in certain forms of cutaneous T-cell lymphoma.

SUMMARYAbsence of CD7 is a stable phenotype in a subset of normal human T cells. Most circulating CD7 ÿ T cells express the CD4CD45RO CD45RA ÿ memory phenotype. We analysed CD4 CD45RA ÿ peripheral blood lymphocytes that were separated into CD7 and CD7 ÿ for their in vitro cytokine secretion in response to different stimuli. The CD4 + CD7 -subpopulation was found to secrete significantly higher levels of IL-5 compared with the CD4 + CD7 + subset upon stimulation with ionomycin/phorbol myristate acetate (PMA) plus anti-CD28 MoAbs. In contrast to IL-5 secretion, IL-4 and interferon-gamma (IFN-°) secretion was not significantly different in CD7 and CD7 ÿ T cells upon stimulation in vitro. The data indicate that the CD4 CD7 ÿ T cell represents the majority of IL-5-secreting cells within the population of CD4 CD45RA ÿ memory T cells. Since CD4 CD7 ÿ T cells were found to be enriched in various skin lesions associated with eosinophilic infiltration, the results of our study support the hypothesis that skin-infiltrating CD7 ÿ T cells are one of the major sources of IL-5 responsible for the development of eosinophilic inflammation in certain skin diseases.

SUMMARYDirected migration of lymphocytes from blood into lymph nodes and organ-associated lymphatic tissue, also referred to as homing, is initiated by T-cell adhesion to specialized high endothelial cells of postcapillary vessels. Here, we demonstrate that selective signal transduction pathways specifically modulate the expression of the cutaneous lymphocyte antigen (CLA), the putative skin-homing receptor, during naive to memory transition of CD4+ T cells in vitro. The results show that the expression of CLA is strongly induced by activation via CD2 [TI 1.1 + T11.2 monoclonal antibodies (mAb)]. Addition of transforming growth factor-fil (TGF-PI), interleukin-6 (IL-6), and, to a lesser extent, IL-2 further enhanced the generation of CLA+ T cells, whereas the induction of this antigen was markedly inhibited by IL-4. Periodic restimulation via CD2 and long-term culture of activated cells in the presence of IL-2 and TGF-BI resulted in stable expression of CLA during a culture period of more than 100 days. In contrast, activation of naive CD4+ T cells via CD3, CD28 or by mitogens induced a rapid naive to memory phenotype transition but a much lower percentage of CLA+ T cells showing only weak expression of the antigen. Furthermore, activation of purified CD4+ memory T cells by CD2 strongly induced expression of activation-related antigens CD25 and HLA-DR, but failed to up-regulate CLA expression. Our results show that primary stimulation conditions highly modulate the development of skin-associated T cells and indicate a new functional role for costimulatory adhesion pathways in regulating the expression of molecules associated with T-cell homing.

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