Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7R alpha-expressing cells.
The common gamma chain cytokines interleukin (IL)-2 and IL-7 are important regulators of T cell homeostasis. Although IL-2 is implicated in the acute phase of the T cell response, IL-7 is important for memory T cell survival. We asked whether regulated responsiveness to these growth factors is determined by temporal expression of the cytokine-specific IL-2 receptor (R) alpha and IL-7Ralpha chains. We demonstrate that IL-2Ralpha is expressed early after priming in T cell receptor-transgenic CD4(+) T cells, whereas IL-7Ralpha expression is lost. In the later stage of the response, IL-7Ralpha is reexpressed while IL-2Ralpha expression is silenced. This reciprocal pattern of IL-2Ralpha/IL-7Ralpha expression is disturbed when CD4(+) T cells are primed in the absence of IL-2 signals. Primed IL-2(-/-) or CD25(-/-) (IL-2Ralpha(-/-)) CD4(+) T cells, despite showing normal induction of activation markers and cell division, fail to reexpress IL-7Ralpha late in the response. Because the generation of CD4(+) memory T cells is dependent on IL-7-IL-7Ralpha interactions, primed IL-2(-/-) or CD25(-/-) CD4(+) T cells develop poorly into long-lived memory cells. Retrovirus-mediated expression of IL-7Ralpha in IL-2(-/-) T cells restores their capacity for long-term survival. These results identify IL-2 as a factor regulating IL-7Ralpha expression and, consequently, memory T cell homeostasis in vivo.
Dooms
Hans
H
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Wolslegel
Kristen
K
Lin
Patricia
P
Abbas
Abul K
AK
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain