Interleukin-2-dependent autocrine proliferation in T-cell development.
Activated T lymphocytes proliferate in response to interleukin-2 (IL-2), which binds to a specific high-affinity receptor (IL-2R). This consists of at least two noncovalently linked polypeptides, p55/IL-2R alpha (Tac) and p75/IL-2R beta. Both molecules bind IL-2 independently, with low and intermediate affinity respectively, but only IL-2R beta is thought to mediate IL-2 signal transduction. Although IL-2R beta seems to be constitutively expressed on resting T lymphocytes, the growth of these T cells is specifically induced by antigenic triggering by the T-cell receptor (TCR), which then results in the transcription of both IL-2 and IL-2R alpha genes. By contrast, activation of the IL-2/IL-2R pathway in the thymus seems to precede the appearance of the TCR, as IL-2R alpha is expressed on T-cell precursors lacking TCR. The basis for IL-2R expression by immature thymocytes, however, remains largely unknown. We show here that IL-2R alpha-negative T-cell precursors constitutively express IL-2R beta and produce their own IL-2. The IL-2/IL-2R beta interaction on these cells induces the expression of IL-2R alpha, leading to high-affinity IL-2R display and cellular proliferation. We suggest that this IL-2-dependent autocrine pathway of growth stimulation plays a key role in the intrathymic development of mature T cells.
Toribio
M L
ML
Centro de Biología Molecular (CSIC), Universidad Autónoma de Madrid, Spain.
Gutiérrez-Ramos
J C
JC
Pezzi
L
L
Marcos
M A
MA
Martínez
C
C
D015703:Antigens, CD / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011994:Recombinant Proteins / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D015703:Antigens, CD; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins