Effects of exogenous IL-2 administration on the homeostasis of CD4+ T lymphocytes.
IL-2 is currently used in HIV-infected patients to treat CD4+ T lymphopenia. In order to document a mechanism accounting for its capacity to restore immune function, we studied the effects of IL-2 administration in mice. IL-2 treatment of C57BL/6 mice for 4 days leads to a transient accumulation of CD4+ T lymphocytes. Whereas memory and activated CD4+ T lymphocytes accumulate after IL-2 treatment in both lymphoid and nonlymphoid organs, naive CD4+ T cells only accumulate in the former. IL-2 transiently increases CD4+ T lymphocyte numbers in lymphopenic IL-7(-/-) mice. Studies in T-cell-reconstituted Rag(-/-) gamma c(-/-) mice and in thymectomized mice demonstrated that IL-2 acts directly on peripheral CD4+ T lymphocytes. In vivo labeling of thymocytes showed that IL-2 also stimulates the release of CD4+ thymocytes from the thymus. Therefore, IL-2 treatment acts centrally and peripherally to increase the size of the naive CD4+ T lymphocyte compartment. This dual activity of IL-2 treatment may influence the quality of restoration of this compartment, especially regarding the ability to reconstitute a normal T lymphocyte repertoire.
Foussat
Arnaud
A
INSERM U131, Cytokines et Immunorégulation, Hêpital Antoine Béclère, Assistance Publique-Hêpitaux de Paris, Institut Paris-Sud sur les Cytokines, 92140 Clamart, France.
Bouchet-Delbos
Laurence
L
Couderc
Jacques
J
Berrebi
Dominique
D
German-Fattal
Michèle
M
Maillot
Marie-Christine
MC
Durand-Gasselin
Ingrid
I
Galanaud
Pierre
P
Di Santo
James P
JP
Emilie
Dominique
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000172:deficiency; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015851:Interleukin-7; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2