Differential production of interleukin-3 in human T lymphocytes following either CD3 or CD2 receptor activation.
Interleukin-3 (IL-3) is expressed in T lymphocytes and stimulates the growth of multipotent hematopoietic progenitors. Little is known, however, about the stimuli that lead to IL-3 protein release. We examined IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression and protein secretion in human T lymphocytes following activation via the TCR/CD3 complex, the CD2 receptor, and the IL-2 receptor. GM-CSF mRNA expression and protein release were found in CD3 and CD2 activated T cells with maximum GM-CSF release following stimulation with IL-2. IL-3 protein release is regulated via the CD2 receptor with virtually no IL-3 release after T cell stimulation via CD3. In contrast, IL-3 mRNA accumulation is more pronounced after CD3 activation than after CD2 activation. This suggests that upregulation of IL-3 protein release following T cell stimulation via CD-2 occurs largely at the translational or posttranslational level. These data also indicate that differential control of cytokine production can occur in response to activation of the alternative T cell receptor. Interaction of the T cell CD2-receptor with its natural ligand LFA-3 expressed on stromal cells might represent a regulatory mechanism for rapid release of IL-3, facilitating proliferation of multipotent hematopoietic cells.
Dilloo
D
D
Department of Pediatric Hematology/Oncology, Heinrich-Heine University Medical Center, Dusseldorf, Germany.
Dirksen
U
U
Schneider
M
M
Zessack
N
N
Buttlies
B
B
Levitt
L
L
Burdach
S
S
D018801:CD2 Antigens / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology*; D002478:Cells, Cultured; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors
D018801:CD2 Antigens; D017252:CD3 Complex; D006133:Growth Substances; D007377:Interleukin-3; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor