T cell immunity required for tumor eradication following combination therapy.

<p>Mice were depleted of specific T cell subsets by systemic administration of antibodies against CD4, CD8 and NK cells and subjected to combined Id2kdN2a cells and α-CTLA-4 antibody treatment strategy (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129237#pone.0129237.g003" target="_blank">Fig 3A</a>) (<b>A</b>) <i>In vivo</i> depletion of CD4+, CD8+ and NK+ cells (n = 5 for all groups) shows that the therapeutic effect of the combined treatment was completely abrogated by CD8+ cell depletion. Mice lacking NK cells were for the most part able to reject their tumors following therapy. CD4+ T cell depletion initially appeared to have minimal adverse effects on the therapeutic vaccine strategy, but after 4 weeks all mice in the CD4 depletion group developed delayed tumors. (<b>B</b>) All CD8+ T cell depleted mice developed tumors at the site of Id2kdN2a cell vaccination as well. (<b>C</b>) Cell infiltrates from the tumors of CD4 depleted mice were stained with anti-CD45-FITC, CD4-APC and FoxP3-PerCPCy5.5 antibodies to identify Treg cells; there was no evidence of Treg cell infiltrate in the late developing tumors from CD4 depleted mice. Purified Treg cells were used as positive control.