Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells

Abstract

The thymus is regarded as the primary site for T-cell lymphopoiesis, but very little is known about the lineage inter-relationships of cells within that organ. At least four subpopulations of mouse thymocytes can be defined on the basis of staining with monoclonal antibodies directed against the T-cell differentiation antigens Lyt-2 and L3T4 (ref. 2). Thus immunocompetent (medullary) thymocytes, like peripheral T cells, express either Lyt-2 (cytotoxic phenotype) or L3T4 (helper phenotype) but not both, whereas non-functional (cortical) thymocytes express both markers. In addition, a small subpopulation comprising 2-3% of cells in the thymus and expressing neither Lyt-2 nor L3T4 has recently been described. The latter cells have the properties of intrathymic 'stem cells' in that they are the first to appear in the embryonic thymus and at least some can be shown to give rise, both in vivo (ref. 4. and our unpublished data) and in vitro, to other thymocyte subpopulations. We show here that 50% of Lyt-2-/L3T4- cells in the adult thymus express receptors for the polypeptide growth hormone interleukin-2 (IL-2) whereas other cells in the thymus do not. Furthermore, immunohistochemical localization studies on frozen sections indicate a disperse distribution of IL-2 receptor-positive cells in both the cortex and medulla. These novel findings have potential implications in the context of current models of differentiation pathways within the thymus.

The IL‐2/IL‐2‐Receptor Complex in the Maturation of Rat T‐Cell Progenitors

“…The current data indicate that rat T-cell precursors (TN cells) express IL-2 receptors, a fact previously denied by other authors (Takacs et al, 1988;Kampinga and Aspinall, 1990), although repeatedly reported in mice, chickens, and humans (Ceredig et al, 1985;Toribio et al, 1989;Fedecka-Brunner et al, 1991). In agreement with our results, Brocke et al (1987) found IL-2Rce-beating cells in the thymus of 16-day-old fetal rats.…”

“…However, much controversy has arisen concerning its role, if any, in the first stages of T-cell development. The expression of individual chains (or,/3, and y) of the IL-2 receptor (IL-2R) on immature thymocytes (Ceredig et al, 1985;Toribio et al, 1989;Kondo et al, 1994;Reya et al, 1996), as well as the ability of these cell subsets to produce IL-2 (Tentori et al, 1988b;Zlotnik et al, 1992) and proliferate in its presence (Ceredig et al, 1989;Toribio et al, 1989;Brooks et al, 1993), *Corresponding author. support the idea that IL-2 may drive the proliferation and the differentiation of T-cell precursors. In fact, the culture of T-cell progenitors with IL-2 promotes their differentiation to TcRcq3, TcRy6, and NK cells (Toribio et al, 1988;De la Hera et al, 1989;Brooks et al, 1993;He and Kabelitz, 1995), and in vivo or in vitro treatments that alter the IL-2/IL-2R complex profoundly modify the T-cell maturation (Jenkinson et al, 1987;Skinner et al, 1987;Tentori et al, 1988a;Plum et al, 1990;Waanders and Boyd, 1990;ZufiigaPflticke and Kruisbeek, 1990;Kroemer et al, 1991;Maslinski et al, 1992).…”

Gene transcription in differentiating immature T cell receptor(neg) thymocytes resembles antigen-activated mature T cells.

“…For example, TN thymocytes at days 14 and 15 of fetal development have been shown to express mRNA for Iblj3, IL4, II.-5, IL-6, II.-7, IFN-3,, and TNF (7)(8)(9). Also expressed are the cell surface molecules: Thy-1, CD2, CD16, CD44, heat stable antigen (HSA), thymic shared antigen (TSA-1), CD18 (LFA-1), CD54 (ICAM-1), Ly-6, CD26 (THAM-1) and the cx chain of the II.-2 receptor (CD25) (10)(11)(12)(13)(14)(15)(16)(17). Markers such as CD25, ICAM-1, CD44, and Ly-6 are prominent on mature T lymphocytes only after TCR activation (15,18,19).…”

The generation and activation of memory class I MHC restricted cytotoxic T cell responses to influenza A virus in vivo do not require CD4+ T cells

“…The MoAbs used were: rat anti-mouse CD8+ (originally from Dr R. Fitch, UniversityofChicago. USA), rat anti-mouse CD4 (25) and anti-mouse Thy 12 (F7D5 clone. Bicester, Oxon, UK).…”