Induction of human T helper cell type 1 differentiation results in loss of IFN-gamma receptor beta-chain expression.
Differential expression of cytokine receptors accounts for an important regulatory mechanism in differentiation of Th1/Th2 subsets. Here, we report that human Th0 and Th2 clones constitutively express transcripts for the IFN-gammaR beta-chain, whereas mRNA for this signaling component of the IFN-gamma receptor is absent in Th1 clones. Activation of T cell clones, however, resulted in a transient induction or enhancement of IFN-gammaR beta-chain mRNA expression in Th1 clones and Th0/Th2 clones, respectively. IL-12-mediated Th1 cell differentiation of naive CD4+, CD45RA+ cord blood T cells, which constitutively express IFN-gammaR beta-chain mRNA, resulted in a loss of expression of this cytokine receptor chain after 6 to 12 days of culture. In contrast, Th2 populations, differentiated from CD4+, CD45RA+ cord blood T cells in the presence of IL-4, continued to express high levels of IFN-gammaR beta-chain transcripts. The loss of IFN-gammaR beta-chain expression in Th1 populations was accompanied by a failure of IFN-gamma to induce the expression of the IFN-gamma-inducible gene, IFN response factor-1, whereas IFN-gamma was effective in inducing IFN response factor-1 mRNA expression in Th0 and Th2 cells. These results indicate that down-regulation of the IFN-gammaR beta-chain correlates with impaired IFN-gamma-induced signaling in Th1 cells. Finally, Th2 populations, generated in the presence of both IL-4 and IFN-gamma, expressed levels of IFN-gammaR beta-chain transcripts similar to those produced by cells differentiated in the presence of IL-4 only, demonstrating that IFN-gamma does not modulate the expression of its receptor. Together, these data indicate that human Th0/Th2 and Th1 subsets, respectively, can be distinguished based on the expression of the IFN-gammaR beta-chain.
Groux
H
H
Department of Human Immunology, DNAX Research Institute, Palo Alto, CA 94304, USA.
Sornasse
T
T
Cottrez
F
F
de Vries
J E
JE
Coffman
R L
RL
Roncarolo
M G
MG
Yssel
H
H
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002999:Clone Cells; D005312:Fetal Blood; D006801:Humans; D017471:Receptors, Interferon / Q000032:analysis*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000096743:Interferon gamma Receptor
D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor