Autocrine and paracrine IL-2 signals collaborate to regulate distinct phases of CD8 T cell memory

Autor: Yevgeniy Yuzefpolskiy, Laura Anne Penny, Florian Martin Baumann, Kendall A Smith, Surojit Sarkar, Vandana Kalia
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:133.1-133.1
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.133.1
Popis: Proliferation is a defining feature of clonal cytotoxic T lymphocyte (CTL) responses upon activation. However, how proliferative events during primary expansion relate to divergent CD8 T cell fate outcomes remains poorly defined. Emerging evidence from our laboratory and others in the field suggest that death-fated effectors undergo more pronounced proliferation compared to memory-fated cells during antigen-driven T cell expansion. Adoptive transfer of activated CD8 T cell-subsets, purified based on their extent of proliferation, showed that in vivo differentiation of CD8 T cells and memory fate are linked to proliferation. We found that the less-divided effector CTL subset preferentially contributed to the central memory lineage. Interestingly, these less-divided memory precursor cells were also programmed to produce more IL-2 compared to their more-divided terminal effector counterparts. How do memory-fated cells that make their own IL-2 (a pro-proliferative cytokine) proliferate less and how does this make them better fit for the long-lived memory lineage? To answer this question, we generated CD8 T cells that could be conditionally ablated for il2. We ablated IL-2 specifically in antigen-specific CD8 T cells, during distinct phases of effector and memory differentiation. Our data showed that while paracrine IL-2 is critical for driving the early in vivo proliferative burst, the programmed life-long autochthonous IL-2 in memory-fated cells was necessary for antigen-independent maintenance, and robust secondary expansion of memory cells. Thus, autocrine and paracrine IL-2 signals collaborate during distinct stages of T cell differentiation to direct diverse CTL lineages through effects on proliferation.
Databáze: OpenAIRE
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