Low dose IL-15 induces snap arming of CD44(low) T lymphocytes in the absence of antigen.
It is widely accepted that naïve T cells require two signals, antigen recognition and co-simulation, to become cytotoxic over the course of 3-5days. However, we observed that freshly isolated murine splenocytes without exposure to antigen become cytotoxic within 24h after culture with IL-15. IL-15 is a cytokine that promotes homeostatic proliferation, maintenance and activation of memory T cells. The induced cytotoxicity, measured by anti-CD3 redirected (51)Cr release, represented the combined activity of T cells regardless of their antigen specificity, and proceeded even when CD44(hi) (memory-associated phenotype) CD8(+) T cells were depleted. Cytotoxic capacity was perforin-dependent and occurred without detectable up-regulation of granzyme B or cell division. After induction, the phenotypic markers for the memory subset and for activation remained unchanged from the expression of resting T cells. Our work suggests that T cells may gain cytotoxic potential earlier than currently thought and even without TCR stimulation.
Tamang
David L
DL
Department of Microbiology and Immunology, University of Nevada, School of Medicine, 1664 N Virginia Street, Reno, NV 89557, USA. david@tamang.org
Alves
Bryce N
BN
Elliott
Viki
V
Fraser
Stephanie A
SA
Redelman
Doug
D
Hudig
Dorothy
D
D000818:Animals; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D048708:Cell Growth Processes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D019409:Interleukin-15 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000276:immunology; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000941:Antigens; D018960:Hyaluronan Receptors; D019409:Interleukin-15; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse