In human blood, 60% to 80% of lymphocytes are mature T cells, and 20% to 30% are mature B cells. Approximately 5% to 10% of the cells do not demonstrate the surface markers associated with either T or B cells. These are NK cells and the rare circulating hemopoietic stem cells (see below). The size differences described above may have functional significance; some of the large lymphocytes may be cells that have been stimulated to divide, whereas others may be plasma cell precursors that are undergoing differentiation in response to the presence of antigen.
Several different types of T lymphocytes have been identified: cytotoxic, helper, suppressor, and gamma/delta ().
The activities of cytotoxic, helper, suppressor, and gamma/delta T lymphocytes are mediated by molecules located on their surface. Immunolabeling techniques have made it possible to identify specific types of T cells and study their function.
 Cytotoxic CD8 T cells serve as the primary effector cells in cell-mediated immunity. CD8 cells are specifically sensitized T lymphocytes that recognize antigens through the TCRs on viral or neoplastic host cells. Cytotoxic CD8 T lymphocytes only recognize antigens bound to MHC I molecules. After the TCR binds the antigen–MHC I complex, the cytotoxic CD8 T cells secrete lymphokines and perforins that produce ion channels in the membrane of the infected or neoplastic cell, leading to its lysis (see Chapter 14, Lymphatic System). Cytotoxic CD8 T lymphocytes play a significant role in rejection of allografts and in tumor immunology.
 Helper CD4 T cells are critical for induction of an immune response to a foreign antigen. Antigen bound to MHC II molecules is presented by antigen-presenting cells such as macrophages to a helper CD4 T lymphocyte. Binding of the TCR to the antigen–MHC II complex activates the helper CD4 T cells. The activated helper CD4 T lymphocytes then produce interleukins (mainly IL-2), which act in an autocrine mode to simulate the proliferation and differentiation of more helper CD4 T lymphocytes. Newly differentiated cells synthesize and secrete lymphokines that affect function as well as differentiation of B cells, T cells, and NK cells. B cells differentiate into plasma cells and synthesize antibody.
 Regulatory (suppressor) T-cells represent a phenotypically diverse population of T lymphocytes that can functionally suppress an immune response to foreign and self-antigen by influencing the activity of other cells in the immune system. The CD4CD25FOXP3 regulator T cells represent a classical example of cells that can down-regulate the ability of T lymphocytes to initiate  immune responses. The FOXP3 marker indicates an  expression of forkhead family transcription factors that are characteristic of many T cells. Furthermore, tumor-associated CD8CD45RO T suppressor cells secrete IL-10 and also suppress T-cell activation. The suppressor T cells may also function in suppressing B-cell differentiation and in regulating erythroid cell maturation in the bone marrow.
 Gamma/delta () T cells represent a small population of T cells that possess a distinct TCR on their surface. As discussed previously, most T cells have a TCR receptor composed of two glycoprotein chains called and  TCR chains. In contrast,  T cells possess TCR receptors made up of one -chain and one -chain. These cells develop in the thymus and migrate into various epithelial tissues (e.g., skin, oral mucosa, intestine, and vagina). Once they colonize an epithelial tissue, they do not recirculate between blood and lymphatic organs. They are also known as intraepithelial lymphocytes. Their location within the skin and mucosa of internal organs allows them to function in the first line of defense against invading organisms.