Tumor expression of major histocompatibility complex antigen (MHC) class I and class II is not essential for the induction of memory T cells. However, induction of MHC class I-restricted effector cytotoxic T cells (CTL) appears dependent on MHC class I expression on tumors. Moreover, the effector function of tumor-specific CTL requires direct recognition of the tumor. In contrast, both the inductive and the effector phases of MHC class II-restricted T cells are independent of MHC class II expression on tumors.
Regulatory T cells (Treg) enriched in FoxP3+, glucocorticoid-induced TNF receptor+, and cytotoxic T-lymphocyte-associated antigen-4+ exert a potential to suppress effector T cells in the periphery. These cells exist in markedly higher proportions within tumor-infiltrating lymphocytes, peripheral blood lymphocytes, and/or regional lymph node lymphocytes of patients with cancer and their frequencies are suggested to be strongly related to tumor progression and inversely correlated with the efficacy of treatment. Tumor-specific Treg cells require ligand-specific activation and cell-to-cell contact to exert their suppressive activity on tumor-specific effector cells (CD8+ cytotoxic T lymphocytes and CD4+ Th cells), which includes decreased cytotoxity, proliferation, and Th1 cytokine secrection. Depletion or blockade of Treg cells can enhance immune protection from tumor-associated antigens that are expressed as self antigens. Recent studies revealed that lymphoma T cells might adopt a Treg profile as well. Studies assessing the influence of chemotherapy on Treg cells have also been included in this review.
Immunoregulatory T cells play a key role in modifying the immune responses to self antigens, tumor antigens, and pathogenic organisms. This review summarizes recent data on naturally occurring CD4+ regulatory T cells that constitutively express CD25 (CD25+ Treg). We examine the markers that can be used to differentiate these cells from effector T cells, what is known about their mode of action in controlling the activity of effector T cells, the antigenic specificity of CD25+ Treg, and their ability to survive and to be selected in vivo. We also summarize specific information on the role of CD25+ Treg in controlling anti-tumor responses, an area were manipulation of this subset holds particular clinical promise.
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