Human CD8+ T lymphocyte subsets that express HLA class I-specific inhibitory receptors represent oligoclonally or monoclonally expanded cell populations.

Abstract

A small percentage of human T lymphocytes, predominantly CD8+ T cells, express receptors for HLA class I molecules of natural killer type (NK-R) that are inhibitory for T-cell antigen receptor (TCR)-mediated functions. In the present study, it is demonstrated that the various NK-R molecules typically expressed by NK cells are also expressed on periheral blood T lymphocytes. These CD3+ NK-R+ cells have a cell surface phenotype typical of memory cells as indicated by the expression of CD45RO and CD29 and by the lack of CD28 and CD45RA. Furthermore, by the combined use of anti-TCR Vf3-specific antibodies and a semiquantitative polymerase chain reaction assay, the TCR repertoire in this CD3+ NK-R+ cell subset was found to be skewed; in fact, one or two V8 families were largely represented, and most of the other Vj8s were barely detected. In addition, analysis of recombinant clones of the largely represented V,B families demonstrated that these Vf3s were oligoclonally or monoclonally expanded.

Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27− Human T Cells

“…NKRs, which have been orginally described on NK cells, can after binding to MHC class I molecules transduce inhibitory signals for cellular cytotoxicity (40). Concordant with previous findings on CD28 Ϫ T cells, we found that CD8 ϩ CD45RA ϩ CD27 Ϫ T cells express a variety of NKR, both of the C-type lectin and Ig superfamily classes (23,24). In healthy individuals the majority of CD8 ϩ CD27 Ϫ T cells express CD45RA but lack CD28 showing that under physiological conditions CD27 Ϫ and CD28 Ϫ subsets represent largely overlapping populations of CD8 ϩ T cells (7).…”

“…Furthermore, in search for potential mechanisms that could control the cytotoxic machinery of these cells in vivo, we found normal expression of CD3⑀ and CD3 chains and absence of CTLA-4 expression. However, in agreement with recent finding on CD28 Ϫ T cells (23,24), a strong increase in the expression of various classes of killer-inhibitory receptors was observed when cells maturate into CD8 ϩ CD45RA ϩ CD27 Ϫ effector T cells (25).…”

“…A complicating finding in appreciating the functional consequences of the expression of these molecules is that the mAb that are being used to detect NKR of the Ig family will also bind to splice variants of these molecules that can act as activating receptors, i.e., killer cell activating receptor (41). Differing with Mingari et al (23), we find highest expression of these regulating receptors on CD45RA ϩ CD27 Ϫ and therefore CD28 Ϫ T cells (7) and not on CD45RA Ϫ CD27 Ϫ T cells. Although it has recently been reported that IL15 can induce CD94/NKG-2A expression on mitogenically activated T cells (42), it is less clear which specific signals do induce the expression of Ig superfamily type NKRs on T cells.…”

Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8+ TCR αβ lymphocytes

“…2c). 3c) nor CD94 heterodimers (data not shown) which confirms that CD94 is acquired after antigenic stimulation [28]. (Fig.…”

Different and Divergent Regulation of the KIR2DL4 and KIR3DL1 Promoters

“…KIR-expressing cells of both the CD8 T cell and NK cell lineages have properties consistent with cellular activation. In particular, KIR ϩ CD8 T cells are believed to be a subset of memory T cells (44,45). Furthermore, the ability of KIR ϩ T cells to survive in culture may be enhanced compared with that of KIR Ϫ cells (46).…”