Persistent expansions of CD4+ CD8+ peripheral blood T cells

Abstract

CD4+ CD8+ cells are present during T cell differentiation in the thymus. Less than 2% of normal T cells that coexpress CD4 and CD8 also are released in the circulation and are present in the peripheral blood. In this study, nine individuals are described that manifested persistent expansions (11% to 43%) of circulating CD4+ CD8+ T cells that in three cases had large granular lymphocyte (LGL) morphology in the absence of either lymphocytosis or overt lymphoproliferative disorders. Southern blot hybridization of enriched CD4+ CD8+ cells with T-cell receptor beta (TCR beta) and TCR gamma probes showed that most cases had the 12-kb Eco RI germinal band deleted or of decreased intensity. In several individuals new TCR beta-specific bands of different intensity and distinct from case to case suggested either monoclonal or oligoclonal and polyclonal expansions. Immunophenotypic analysis showed that in 7 out of 9 cases the CD4+ CD8+ T cells presented with CD8 dim expression. Furthermore, all the CD4+ CD8+ cells did not express many of the known activation antigens (low or absent CD25, CD38, CD71, HLA-DR), whereas they expressed high levels of CD2, CD29, CD56, and CD57. In addition, the CD4+ CD8+ cells of 5 out of 9 subjects coexpressed CD45RA and CD45RO suggesting that these cells might be “frozen” in an intermediate state between naive and memory T cells. In conclusion, the present CD4+ CD8+ cases fall within a larger spectrum of disorders ranging from apparently normal to reactive or proliferative situations and encompassing cells with LGL morphology or LGL-associated antigens expression either in the presence or in the absence of absolute lymphocytosis that deserve careful follow-up investigations.

Persistent oligoclonal CD4dimCD8+T cells in peripheral blood

“…Moreover, in some cases, the dot plot had a very homogeneous distribution, suggesting that only a restricted number of specificities was concerned. This homogeneity was confirmed with TCR clonotyping in accordance with a previous report (1) and most probably corresponds to at least an oligoclonal expansion of these cells.…”

“…They seem to be persistent and were observed on repeated analyses in patients periodically tested over months or years of follow‐up (our experience) (1). It was difficult to define reference values because the dot plot appearance was much influenced by lymphocytosis.…”

“…However, it is usually admitted that mature conventional T cells express in a mutually exclusive manner only one of them in relation to their helper (CD4 + ) or cytotoxic (CD8 + ) activity. Recent phenotyping techniques using multiparametric labeling have led to occasional observations of a minor group of CD3 + T cells that coexpress both coreceptors in peripheral blood (1–3). On these unconventional T cells, each coreceptor is expressed at different levels of fluorescence intensity in flow cytometry.…”

Study of CD4+CD8+ Double positive T‐lymphocyte phenotype and function in Indian patients infected with HIV‐1

“…Owing to the tight regulation of thymic T cell development process, double positive T cells were believed to arise due to premature release of these CD4+CD8+ T cells from thymus to periphery [Bonomo et al, 1994; Jimenez et al, 2002]. However, growing body of evidences suggests otherwise, and studies have been undertaken to elucidate role of these cells in viral pathogenesis [Sala et al, 1993; Tonutti et al, 1994; Suni et al, 2001; Howe et al, 2009]. Of late, several studies have reported an increased frequency of these atypical cells in pathological conditions.…”

Expression of CD8α identifies a distinct subset of effector memory CD4+ T lymphocytes

“…CD4 + CD8 + T lymphocytes represent a minor subset of circulating T cells coexpressing both CD4 and CD8 molecules on their surface. In human peripheral blood, CD4 + CD8 + T cells are relatively infrequent, constituting on average 1-2% of CD3 + lymphocytes, 1-3 but they have been observed at increased frequencies in some normal subjects [4][5][6][7] and in individuals with a wide range of diseases such as T-and B-cell leukaemia, 8,9 autoimmune dis-eases 10 and bacterial or viral infections. [11][12][13] CD4 + CD8 + T cells have also been described in other species, including mice, 14 rats, 15 swine 16 and cynomolgus macaques 17 and in some species they represent up to 20-60% of circulating T lymphocytes.…”