18). In addition, TCR engagecharacteristic of 'memory' T lymphocytes. 1-5 A high percentment results in Zap70 activation after its binding to the tyrosylage of the malignant cells constitutively express BE2, a late phosphorylated immunoreceptor tyrosine-based activation activation marker of 78 kDa, that appears on cloned normal motifs (ITAMs) of the chains and the CD3 complex 23,24 (for T cells only after stimulation with specific antigen, and on review see Ref. 25) and in rapid tyrosine phosphorylation and freshly isolated normal T cells in response to mitogens, 6,7 sugactivation of Syk. 26 The signaling initiated by TCR activation gesting that CTCL cells have been activated by their surroundis transmitted from the cell membrane through the cytoplasm ing dermal environment. Since CTCL lymphocytes can proto the nucleus and induces quiescent T cells to undergo cell liferate in the cutaneous compartment but are extremely division and maturation, processes critical for clonal expandifficult to cultivate in vitro, their neoplastic growth appears sion and initiation of the immune responses. to reflect in vivo stimulation, possibly through their TCR, orWe selected for investigation several immediate key reacantigen-independent pathways or cytokines. IL-7 might be one tions essential for T cell receptor-mediated signal transducof the required growth factors for CTCL cells in the skin since tion, proliferation and effector functions. Our results, based transgenic mice constitutively producing IL-7 developed on analysis of a limited sample of CTCL cells (from four extensive dermal infiltration followed by dermotropic lympatients), show nevertheless, common characteristics, ie phoma. 8,9 However, although IL-7 is produced by keradeficiencies in critical immediate functions associated with tinocytes, it is a weak in vitro CTCL mitogen, 10 and purified TCR activation. These include molecules participating in populations of CTCL cells were sustained in culture for only events proximal and distal to the TCR such as: (1) reduced a short period (such as a week) by mixtures of cytokines that levels of basal and stimulated tyrosyl-phosphorylated proteins include IL-7 and IL-2. 11,12 belonging to a wide range of signaling molecules; The preferential expression of CD45RO and the clonal TCR (2) suppressed specific activity of membrane-bound Csk and rearrangement suggest that CTCL clones have encountered a Lck; (3) failure to activate membrane-bound PTPase; (4) failure to activate Zap70 and to induce its association with the TCR chain; and (5) reduced expression and activity of Syk. LimitedCorrespondence: R Halaban, Department of Dermatology, Yale Unicomparative analysis with the CD4 + /CD45RO + subpopulation
Monoclonal antibodies to human T cells permit the characterization of the surface phenotype of cutaneous T cell lymphoma (CTCL). The majority of CTCL cells are reactive with OKT1 and OKT3 monoclonals, which identify peripheral T cells and mature thymocytes. The neoplastic cells also react with OKT4, which recognizes the inducer T cell subset; they are, however, unreactive with OKT5 monoclonal, which identifies cytotoxic/suppressor T cell subsets. These data are in agreement with previous functional studies demonstrating that CTCL is a neoplasm of inducer (helper) T cells.
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