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Heterogeneity of the human CD4+ T-cell population: two distinct CD4+ T-
cell subsets characterized by coexpression of CD45RA and CD45RO isoforms
D Hamann, PA Baars, B Hooibrink and RW van Lier
Department of Clinical Viro-Immunology, Central Laboratory of the
Netherlands Red Cross Blood Transfusion Service, Amsterdam, The
Netherlands.
Activation of unprimed CD4+CD45RA+/RO- T cells results in a gradual loss of
CD45RA expression concomitant with the acquisition of CD45RO. It has been
suggested that this conversion occurs in vivo through a
CD45RAbright/RObright stage. Next to this small CD45RAbright/RObright
subset (Dbright), a larger subpopulation that expresses both RA and RO
isoforms at low levels (Ddull) can be found in the circulating CD4+ T- cell
population of all donors. The properties of the latter population are
largely undefined. Here, we show that Ddull cells have an intermediate
phenotype for antigens such as CD31, CD621, CD58, and CD95 that are
differentially expressed on unprimed versus primed T cells. In addition,
they are able to provide help for B-cell differentiation and contain
substantial numbers of tetanus toxoid (TT)-specific precursor cells.
Remarkably, both intracellular cytokine staining and analysis of T-cell
clones showed that Ddull cells and CD45RO+ T cells produce comparable high
amounts of both interferon (IFN)-gamma and interleukin (IL)-4, which
clearly distinguishes them from CD45RA+ and Dbright T cells. Finally,
prolonged culture of sorted Ddull cells in a mixture of IL-2, IL-6, and
tumor necrosis factor (TNF)-alpha showed that about half of the population
retained the Ddull phenotype. Part of the cells upregulated the CD45RA
isoform, whereas only a minority switched to single CD45RO expression. Our
findings indicate that the Ddull population contains primed T cells, some
of which may reacquire an "unprimed" phenotype in the absence of antigenic
stimulation.
Volume 88,
Issue 9,
pp. 3513-3521,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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