Role of IL-2 in rat fetal thymocyte development

Abstract

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high-affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR-P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.

Appearance and Maturation of T‐Cell Subsets During Rat Thymus Ontogeny

“…Presumably, the distinct expansion of these mature T-cell subsets is correlated with differential responses to cytokines, for which they express specific receptors, as previously pointed out in humans (He and Kabelitz, 1993). This selective response has been recently confirmed by us in either IL-2-or IL-7-treated rat FTOC (Varas et al, 1997a(Varas et al, , 1997b.…”

“…The nature of the signal(s) promoting the increased thymocyte proliferation in perinatal thymus is yet unknown. Ceredig and Waltzinger (1990) (Varas et al, 1997a(Varas et al, , 1997b.…”

Regulation of Mu Opioid Receptor Expression in Developing T Cells

“…While there is some suggestion that IL-2 promotes developing T cell growth (Varas et al 1997; Tentori et al 1988), recent evidence shows that IL-2 is required for the development of T regulatory cells (Malek et al 2008), and there is ample evidence that this cytokine contributes to negative T cell selection in the thymus (Bassiri et al 2001; Porter et al 2000). Similarly, IFNγ also promotes apoptosis, and anti-IFNγ antibody reverses this effect, suggesting that these two cytokines have a suppressive effect on developing T cells (Groux et al 1993).…”

Autonomic innervation of immune organs and neuroimmune modulation

“…Through apoptosis VIP can affect T cell development participating in the generation and maturation of immune cells and in thymic response to stressful conditions. Immunomodulatory activity of VIP is mediated, at least in part, by production of cytokines which are known to control intrathymic T cell development (Ganea, 1996; Varas, Vicente, Romo & Zapata, 1997; Reya, Bassiri, Biancaniello & Carding, 1998). VIP inhibits also IL‐2 and IL‐4 production from murine thymocytes (Xin, Tang & Ganea, 1994; Xin et al.…”