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The Mature, Mitogen‐Responsive, Human Thymocyte Population Comprises Two Functionally Distinct T‐Cell Subsets Differing in Exogenous Interleukin Requirements for Mitogenesis and in Sensitivity to Glucocorticoids
Author(s) -
RANELLETTI F.O.,
PIANTELLI M.,
CARBONE A.,
MAGGIANO N.,
LAROCCA L. M.,
AIELLO F. B.,
MUSIANI P.
Publication year - 1986
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1986.tb03072.x
Subject(s) - thymocyte , percoll , biology , phytohaemagglutinin , interleukin 2 , population , differential centrifugation , receptor , lymphokine , endocrinology , mitogen activated protein kinase , microbiology and biotechnology , medicine , t cell , centrifugation , immunology , biochemistry , signal transduction , antigen , immune system , demography , sociology , stimulation
Human thymocytes were separated into 10 fractions by continuous Percoll density gradient centrifugation. Almost all the cells able to proliferate in response to phytohaemagglutinin (PHA) and about 80% of the thymocytes carrying the mature T3 marker were contained within the first two lightest fractions (Fr1 and Fr2), However, cells in Fr1 and in Fr2 were clearly different in terms of their interleukin requirement for mitogenesis. i.e., in the presence of interleukin‐1 (IL‐1). Fr1 thymocytes showed proliferative responses to PHA that were three to five times greater than those of the Fr2 cells, whereas in the presence of exogenous IL‐2 both Fr1 and Fr2 cells bad mitogenic responses of a similar magnitude. These differences could not be explained by accessory cell contamination or by different kinetics of the proliferative responses. Furthermore, in the presence of exogenous IL‐1. Fr1 thymocytes showed a greater capacity for producing IL‐2, In contrast, there was no difference in the expression of functional IL‐2 receptors between the two fractions. It can be concluded that the mature thymocyte subpopulation contains at least two functionally distinct subsets, which differ in density, and that during intrathymic maturation the capacities to produce and to respond to IL‐2 do not develop simultaneously. Although both the number and the binding characteristics of glucocorticoid (GC) receptor sites did not differ significantly between Fr1 and Fr2 thymocytes. dexamethasone was more effective in inhibiting the PHA‐induced mitogenesis of Fr2 than of Fr1 cells. Thus, the GC sensitivity of T‐cell mitogenesis is not directly correlated with receptor‐related variables. In contrast with observations made on peripheral T cells, the inhibitory activity of GC on thymocyte mitogenesis was only partially reversed by the addition of exogenous IL‐2, Thus, the inhibitory action of GC on thymocyte mitogenesis cannot be explained only by the steroid‐induced inhibition of IL‐1‐IL‐2 production; it must also be due to a GC‐inhibitory effect on the IL‐2‐responsive cell proliferation.

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