IL-15 induces type 1 and type 2 CD4+ and CD8+ T cells proliferation but is unable to drive cytokine production in the absence of TCR activation or IL-12 / IL-4 stimulation in vitro.
Interleukin 15 (IL-15) is a pleiotropic cytokine produced principally by monocytes and affects both innate and acquired immunity. It has been shown that IL-15 is essential for the proliferation and maintenance of CD8+ memory cells but has little or no effect on naive CD8+ cells or CD4+ T cells. We report here, using an in vitro culture system of antigen-specific OVA TCR transgenic T cells as well as normal mouse T cell activated with anti-CD3 antibody that IL-15, at high concentrations, induced proliferation of both naive and memory CD4+ and CD8+ cells. IL-15 also enhanced the differentiation of type 1 (IFN-gamma-producing) and type 2 (IL-5-producing) CD4+ and CD8+ T cells under IL-12 and IL-4 driving conditions, respectively. However, IL-15 alone was not efficient in stimulating cytokine production of these cells in the absence of T cell subset driving cytokines (IL-12 or IL-4) and / or simultaneous TCR activation. Together, these results demonstrate that IL-15, at high dose, is a pan-T cell growth factor. The apparent requirement of IL-15 for the maintenance of memory CD8+ cell in vivo may reflect the exceptionally restricted nature of this subpopulation of cells for IL-15. The inability of IL-15 alone to stimulate cytokine synthesis also suggests that IL-15 on its own does not drive antigen-specific T cells to exhaustion. The levels of these cells are maintained by IL-15 and they are only mobilized to carry out effector functions when subsequently confronted with specific pathogens.
Niedbala
Wanda
W
Department of Immunology and Bacteriology, University of Glasgow, Glasgow G11 6NT, Scotland, GB.
Wei
Xiaoqing
X
Liew
Foo Y
FY
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007156:Immunologic Memory; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D019409:Interleukin-15; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018664:Interleukin-12; D015847:Interleukin-4; D010047:Ovalbumin