Killing of targets by effector CD8$^ $T cells in the mouse spleen follows the law of mass action - Quantitative Biology > Quantitative MethodsReport as inadecuate




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Abstract: It has been difficult to measure efficacy of T cell-based vaccines and tocorrelate efficacy of CD8$^+$T cell responses with protection against viralinfections. In part, this difficulty is due to our poor understanding of the invivo efficacy of CD8$^+$T cells. Using a recently developed experimental methodof in vivo cytotoxicity we investigated quantitative aspects of killing ofpeptide-pulsed targets by effector and memory CD8$^+$T cells, specific to threeepitopes of lymphocytic choriomeningitis virus LCMV, in the mouse spleen. Byanalyzing data on killing of targets with varying number of epitope-specificeffector and memory CD8$^+$T cells, we find that killing of targets byeffectors follows the law of mass-action, that is the death rate ofpeptide-pulsed targets is proportional to the frequency of CTLs in the spleen.In contrast, killing of targets by memory CD8$^+$T cells does not follow themass action law because the death rate of targets saturates at high frequenciesof memory CD8$^+$T cells. For both effector and memory cells, we also find nosupport for a killing term that includes the decrease of the death rate oftargets with increasing target cell density. Importantly, we find that at lowCD8$^+$T cell frequencies, effector and memory CD8$^+$T cells on the per capitabasis are equally efficient at killing peptide-pulsed targets. Our frameworkprovides the guideline for the calculation of the level of memory CD8$^+$Tcells required to provide sterilizing protection against viral infection. Ourresults thus form a basis for quantitative understanding of the process ofkilling of virus-infected cells by T cell responses in tissues and can be usedto correlate the phenotype of vaccine-induced memory CD8 T cells with theirkilling efficacy in vivo.



Author: Vitaly V. Ganusov, Daniel L. Barber, Rob J. De Boer

Source: https://arxiv.org/







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