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

Abstract

To better characterize the cellular source of lymphotactin (XCL1), we compared XCL1 expression in different lymphocyte subsets by real-time PCR. XCL1 was constitutively expressed in both PBMC and CD4+ cells, but its expression was almost 2 log higher in CD8+ cells. In vitro activation was associated with a substantial increase in XCL1 expression in both PBMC and CD8+ cells, but not in CD4+ lymphocytes. The preferential expression of XCL1 in CD8+ cells was confirmed by measuring XCL1 production in culture supernatants, and a good correlation was found between figures obtained by real-time PCR and XCL1 contents. XCL1 expression was mostly confined to a CD3+CD8+ subset not expressing CD5, where XCL1 expression equaled that shown by γδ+ T cells. Compared with the CD5+ counterpart, CD3+CD8+CD5− cells, which did not express CD5 following in vitro activation, showed preferential expression of the αα form of CD8 and a lower expression of molecules associated with a noncommitted/naive phenotype, such as CD62L. CD3+CD8+CD5− cells also expressed higher levels of the XCL1 receptor; in addition, although not differing from CD3+CD8+CD5+ cells in terms of the expression of most α- and β-chemokines, they showed higher expression of CCL3/macrophage inflammatory protein-1α. These data show that TCR αβ-expressing lymphocytes that lack CD5 expression are a major XCL1 source, and that the contribution to its synthesis by different TCR αβ-expressing T cell subsets, namely CD4+ lymphocytes, is negligible. In addition, they point to the CD3+CD8+CD5− population as a particular T cell subset within the CD8+ compartment, whose functional properties deserve further attention.

International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

“…However, even after the discovery and initial characterization of XCR1, the precise cell types that express XCR1 long remained unknown because of the lack of good reagents for surface XCR1. Although XCR1 mRNA was reported to be expressed by CD8 + T cells, NK cells, and neutrophils, consistent with some but not all of the published results for the presumed target cells of XCL1 Cairns et al, 2001;Huang et al, 2001;Stievano et al, 2003;Luttichau et al, 2007), the actual levels of expression were very low. Thus, these data may be due mostly to PCR amplification of contaminating DNA in the RNA samples.…”

“…XCL1 is now known to be produced by activated CD8 + T cells, dendritic epidermal invariant Vg3Vd1 T cells, intestinal intraepithelial gd T cells, and NK cells (Boismenu et al, 1996;Muller et al, 1995;Hedrick et al, 1997). Human CD8 + ab T cells, especially a minor subpopulation lacking CD5 expression, were reported to be the major producer of XCL1 (Stievano et al, 2003). Activated CD8 + T cells and NK cells secrete XCL1 together with CCL3, CCL4, and CCL5, suggesting some functional cooperation among these chemokines (Dorner et al, 2002).…”

T Cell Epitope Immunotherapy Induces a CD4+ T Cell Population with Regulatory Activity

“…Interestingly, the increases observed on CD8 + T cells were partly due to a reduction in the size of the CD8 + CD5 neg T cell population. A distinct CD8 + CD5 neg T cell population that accounts for 3%–10% of the total CD8 + T cell population in healthy donors has previously been described [48] and appears to be the main producer of lymphotactin (XCL-1) [49]. As the average size of CD8 + CD5 neg T cell populations in the allergic asthmatic patients in our study is substantially larger (23.2% of the total CD8 + T cells), it is tempting to speculate that this is further evidence for a dysregulated immune response associated with allergic disease.…”

Expressions of lymphotactin and its receptor, XCR, in Lewis rats with experimental autoimmune anterior uveitis

“…Lymphotactin (XCL), the sole member in the C chemokine family, has only two of the four cysteines conserved in other chemokines, and also has a C-terminal sequence much longer than those of other chemokines [10,11]. With a dominant expression in activated CD8 + T cells and activated natural killer cells [12], lymphotactin is a powerful attractant of lymphocytes, particularly T-cells and natural killer (NK) cells, but is inactive for inducing the migration of neutrophils and monocytes [13,14]. Such target cell specificity is unique among the chemokine superfamily, suggesting the existence of a lymphotactinspecific receptor, XCR, which is a specific G proteincoupled receptor expressed in circulating lymphocytes and NK cells [15,16].…”