IL-2 induces a competitive survival advantage in T lymphocytes.
The acquisition of long-term survival potential by activated T lymphocytes is essential to ensure the successful development of a memory population in the competitive environment of the lymphoid system. The factors that grant competitiveness for survival to primed T cells are poorly defined. We examined the role of IL-2 signals during priming of CD4(+) T cells in the induction of a long-lasting survival program. We show that Ag-induced cycling of CD4(+) IL-2(-/-) T cells is independent of IL-2 in vitro. However, IL-2(-/-) T cells failed to accumulate in large numbers and develop in effector cells when primed in the absence of IL-2. More importantly, Ag-activated IL-2(-/-) T cells were unable to survive for prolonged periods of time after adoptive transfer in unmanipulated, syngeneic mice. IL-2(-/-) T cells exposed to IL-2 signals during priming, however, acquired a robust and long-lasting survival advantage over cells that cycled in the absence of IL-2. Interestingly, this IL-2-induced survival program was required for long-term persistence of primed IL-2(-/-) T cells in an intact lymphoid compartment, but was unnecessary in a lymphopenic environment. Therefore, IL-2 enhances competitiveness for survival in CD4(+) T cells, thereby facilitating the development of a memory population.
Dooms
Hans
H
Department of Pathology, University of California San Francisco School of Medicine, San Francisco, CA 94143, USA.
Kahn
Estelle
E
Knoechel
Birgit
B
Abbas
Abul K
AK
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016685:Mitomycin / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; C111390:OVA 323-339; D010446:Peptide Fragments; D016685:Mitomycin; D010047:Ovalbumin