Low dose IL-15 induces snap arming of CD44 low T lymphocytes in the absence of antigen

• Published in: Cellular immunology Vol. 251; no. 2; pp. 93 - 101
• Main Authors: Tamang, David L., Alves, Bryce N., Elliott, Viki, Fraser, Stephanie A., Redelman, Doug, Hudig, Dorothy
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2008
• Subjects: Cytotoxic T lymphocyte; Granzyme B; IL-15; IL-2; Granzyme B; IL-15; IL-2; Cytotoxic T lymphocyte
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2008.04.007

It is widely accepted that naïve T cells require two signals, antigen recognition and co-simulation, to become cytotoxic over the course of 3–5 days. However, we observed that freshly isolated murine splenocytes without exposure to antigen become cytotoxic within 24 h 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 51Cr 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.