Differentiation potential of subsets of CD4−8− thymocytes

Abstract

Precursor T cells in the thymus are contained within a subpopulation of thymocytes that lack the markers CD4 and CD8. We have examined the heterogeneity of these cells by flow cytometric analysis, and defined four subpopulations using the cell surface markers Thy-1, J11d and the IL-2 receptor (IL-2R). The J11d+ subset of CD4-8- cells all bear the antigen Thy-1, and some express the IL-2R. Staining and RNA analysis of J11d+ cells suggest that some express receptors of the CD3 gamma delta type, but none express CD3 alpha beta receptors. In fetal thymus organ culture, the J11d+ cells diversify to form 'cortical type' CD4+8+ cells and 'medullary type' cells expressing either CD4 or CD8; in vivo they repopulate the thymus of an irradiated host and seed the periphery with T cells. In contrast, the J11d- subset of CD4-8- thymocytes do not all bear Thy-1 and none express the IL-2R, but some express antigen receptors of the CD3 alpha beta type. They have more limited diversification potential in organ culture, and in vivo fail to recolonize the irradiated host in a homing-independent assay. We conclude that they are not precursor T cells, but rather a side-branch from the main line of T cell differentiation.

A murine early thymocyte developmental sequence is marked by transient expression of the interleukin 2 receptor.

“…Previous studies in this area have given discordant results (9,14,15,18), which we now attribute, in part, to the use of insufficient surface markers to delineate all separate subpopulations involved. Our present studies use six surface markers in all, which makes the description of subpopulations unwieldy but is necessary to resolve the discrepancies.…”

“…An important implication of the latter suggestion is that there should exist among the double negatives distinct precursors capable of giving rise to only single positives (one or both types) or only double positives. Four markers that allow further useful subdivision of the double-negative thymocytes are the T-cell antigen receptor (TCR) and the associated CD3 complex (4)(5)(6)(7)(8), phagocytic glycoprotein 1 (Pgp-1) (9-11), heat-stable antigen (HSA) recognized by the monoclonal antibodies (mAbs) B2A2, Ml/69, and Jl1d (10,(12)(13)(14)(15), and the 55-kDa chain of the interleukin 2 receptor (IL-2R) recognized by mAbs such as PC.61 (9)(10)(11)(12)(15)(16)(17).…”

Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice

“…[11][12][13][14][15][16] To identify NKT cells, 2-color staining for CD3 and NK1.1 was conducted (Fig. 4).…”

T cell receptor vβ repertoire of double‐negative α/β t cells in patients with systemic sclerosis

“…These data indicate that sorted DN cells include neither CDCpositive nor CD8-positive T cells. In autoimmune-prone mice, such as the MRLlprllpr mouse, DN T cells have been found in large numbers in lymph nodes, and have shown a strikingly limited TCR V, repertoire, in which V, chains encoded by the V&3 gene family are expressed at an unusually high frequency in these species (3,11,12). DN dj3 T cells in these mice might function as autoreactive T cells, in collaboration with CD4-positive T cells, which could produce interleukin-4 and interferon-y (13).…”

“…A subset of TCR d p T cells that do not express the CD4 and CD8 molecules has been detected in mice (3). In autoimmune-prone mice such as MRL-lprDpr and C3H/HeJ-gld/gld, many double-negative (DN) d p T cells accumulate in peripheral lymph nodes.…”