As previously described, CD4 help induced the differentiation of highly proliferating memory-like CD8+ T cells into effectors as demonstrated by the dowregulation of CD62L and the upregulation of CD25 in control mice (Fig. 4C) [29].
This finding contrasts sharply with previous analyses, in which the frequencies of proliferating CD8+ memory T cells in the BM were calculated according to BrdU incorporation into cellular DNA, in cells undergoing active DNA synthesis [ 8, 12, 13].
T lymphocytes recognise cell antigens only from major histocompatibility complex molecules and proliferate into memory and effector T cells.
Activated cytotoxic T cells begin to proliferate into memory cytotoxic T cells or effector cytotoxic T cells.
Some of these proliferating cells become memory helper T cells that contribute to immunological memory and respond quickly to future infections by the same pathogen.
Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4+ T cells in effective antitumor immunity and reveal that CD4+ T cells induce more durable immune-mediated tumor control than CD8+ T cells.
Here, infected B cells may express transformation-associated viral genes and proliferate [44], [46], [47], but the only infected cells that enter the circulating peripheral blood are those with a non-proliferating memory B-cell phenotype and those with repressed expression of transformation-associated viral genes [48], [49].
Hypothetically, vaccination with VXM01 should lead to breakdown of existing tumor vasculature and support the development of an immune memory against proliferating endothelial cells.
Proliferating cells retained a central memory phenotype (Fig. 4C).
To analyze the memory phenotype of proliferating cells we stained the cells with anti-CD3 APCCy7, anti-CD4 PerCP, anti-CD8 PECy7, anti-CD44 PE and anti-CD62L APC monoclonal antibodies (BD Pharmingen).
