Contrasting effect of transforming growth factor type beta 1 (TGF-beta 1) on proliferation and interleukin-2 receptor expression in activated and rapidly cycling immature (CD3-CD4-CD8-) thymocytes.
Transforming growth factor beta (TGF-beta) is a cytokine with immunoregulatory properties that acts negatively on T lymphocyte proliferation. However, with the EL 4-6.1 variant of the murine thymoma EL 4 activated with phorbol ester and/or interleukin-1 (IL-1), we recently found that it up-regulates interleukin-2-receptor (IL-2R) expression. Since EL 4-6.1 cells share phenotypic and functional characteristics with the immature thymic subset lacking CD4 and CD8 accessory molecules (DN), we investigated the effect of TGF-beta 1 on the IL-2R 55kD alpha chain expression and proliferation of activated DN cells and especially in DN cells that do not express CD3. We observed that TGF-beta 1 was able to increase both the percentage of CD3-DN cells expressing IL-2R alpha chains and the expression of IL-2R alpha chain in these cells. This stimulatory effect of TGF-beta 1 was distal from early transduction events. In addition, TGF-beta 1 was found to modulate CD3-DN cell proliferation. During differentiation in the thymus, CD3-DN cells transiently express the IL-2R alpha chain of the IL-2R and these IL-2R+ CD3-DN cells are preprogrammed to down-regulate the IL-2R alpha chain and up-regulate the CD4 and CD8 accessory molecule. We thus also tested the effect of TGF-beta 1 on IL-2R alpha chain expression in these in vitro differentiating CD3-DN cells. We found that TGF-beta 1 neither significantly affected IL-2R expression nor changed CD4 or CD8 expression. Hence, in CD3-DN cells, the effect of TGF-beta 1 on IL-2R expression seems to be restricted to proliferating cells.
Dupuy d'Angeac
A
A
Unité INSERM 291, Montpellier, France.
Rème
T
T
Monier
S
S
Gao
Q
Q
Duperray
C
C
Jullien
P
P
Dornand
J
J
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation
D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate