Phenotypic and functional characterization of human cytolytic T cells lacking expression of CD5.

Abstract

Although the CD5 (T1) antigen was initially described as a pan-T cell membrane glycoprotein, we report that 14 of 40 normal individuals were found to have 5% or greater of their blood mononuclear cells characterized as CD3 (T3)+ but CDSby dual immunofluorescence flow cytometry. These cells expressed normal quantities of surface CD3 and CD2 but low levels of CD7, were CD8' and CD4-, and CD16-. In order to determine whether cells of this phenotype were functional, six CD5-cytolytic T lymphocyte (CTL) clones isolated from normal individuals were studied. The CDS-CTL clones all demonstrated normal cytolytic activity against appropriate target cells. Monoclonal antibodies (MAbs) directed against CD3, CD8, CD2, and lymphocyte function-associated antigen 3, but not against CD5, inhibited cytolytic activity. Changes in intracellular calcium (ICa2+I,) in response to anti-CD5 and anti-CD3 MAbs were measured. Stimulation by anti-CD5 MAb alone did not give rise to a change in ICa2+I. However, under conditions of limiting concentrations of anti-CD3 MAb, preincubation of normal CD5', but not CD5-, clones with anti-CD5 MAb led to a dramatic enhancement in the ability of anti-CD3MAb to elicit a rise in ICa211. We conclude that CD5-T lymphocytes represent a normal lymphoid phenotype. Although CD5 may be involved in T cell activation when present, these CD5-CTL clones appear to express normal cytolytic activity.

CD8+αβ+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes

“…The size of this subset in the different lymphoid compartments was small; in peripheral blood, according to previously published data (41,42), the percentage of CD3 ϩ CD8 ϩ CD5 Ϫ cells within the CD8-expressing population was 5.2 Ϯ 2.8 (range, 10.2-1.0); the size of this subset was significantly lower in lymph nodes (1.3 Ϯ 0.8; range, 2.5-0.5; p Ͻ 0.01, according to the Mann-Whitney test) and tonsils (3.5 Ϯ 3.0; range, 7.9 -1.0); in these latter, probably due to the small number of samples examined, the difference from PBMC was not significant ( p ϭ 0.43).…”

“…2 and 5). Thus, XCL1 expression by ␣␤ ϩ T cells seemed to be relatively restricted to this small subset, which accounts for ϳ3-10% of the CD8 ϩ T cells in the circulation of healthy donors (40,42). Although this population has been characterized to some extent, information on its phenotypic and functional properties is incomplete, and its function and physiologic significance are unknown.…”

Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations

“…However, the 5 immunophenotypic features of T cells in other subtypes of HLH have not been fully characterized. Human CD5 is a membrane glycoprotein that belongs to the scavenger receptor cysteine-rich family of receptors [6][7][8][9]. It is expressed on thymocytes, mature peripheral T cells and a small population of B cells, and is involved in the modulation of antigen-specific receptor-mediated activation and differentiation signals [6][7][8][9].…”

“…Human CD5 is a membrane glycoprotein that belongs to the scavenger receptor cysteine-rich family of receptors [6][7][8][9]. It is expressed on thymocytes, mature peripheral T cells and a small population of B cells, and is involved in the modulation of antigen-specific receptor-mediated activation and differentiation signals [6][7][8][9]. It has recently been reported that CD5 is recruited and colocalized with CD3 at the immunological synapse and inhibits T-cell receptor (TCR) signaling in T cells without interfering with immunological synapse formation [10].…”

Stimulation of CD5 enhances signal transduction by the T cell antigen receptor.

“…CD5 MAb can also enhance CD3/Ti-mediated Ca>2 influx, an effect that does not require crosslinking (12,13). CD5, therefore, may either independently regulate a Ca 2 influx mechanism or influence signaling by CD3/Ti.…”