T cells can be distinguished from other types of lymphocytes by their cell surface phenotype, based on the pattern of expression of various molecules, and by differences in their biologic functions. All mature T cells express certain cell surface molecules, such as the cluster determinant 3 (CD3) molecular complex and the T-cell antigen receptor, which is found in close association with the CD3 complex. T cells recognize antigen through the cell surface T-cell antigen receptor (TCR). The structure and organization of this molecule are similar to those of antibody molecules, which are the B-cell receptors for the antigen. During T-cell development, the T-cell receptor gene undergoes gene arrangements similar to those seen in B cells, but there are important differences between the antigen receptors on B cells and T cells. The T-cell receptor is not secreted, and its structure is somewhat different from that of antibody molecules. The way in which the B-cell and T-cell receptors interact with antigens is quite different. T cells can respond to antigens only when these antigens are presented in association with MHC molecules on antigen-presenting cells. Effective antigen presentation involves the processing of antigen into small fragments of peptide within the antigen-presenting cell and the subsequent presentation of these fragments of antigen in association with MHC molecules expressed on the surface of the antigen-presenting cell. T cells can respond to antigens only when presented in this manner, unlike B cells, which can bind antigens directly, without processing and presentation by antigen-presenting cells (75).
There are two major subsets of mature T cells that are phenotypically and functionally distinct: T-helper/inducer cells, which express the CD4 cell surface marker, and the
T-cytotoxic cells, which express the CD8 marker. The expression of these markers is acquired during the passage of T cells through the thymus. CD4 T cells can provide help to B cells, resulting in the production of antibodies by B cells, and interact with antigen presented by antigen-presenting cells in association with MHC class II molecules. CD4 T cells can act as helper cells for other T cells. CD8 T cells include cells that are cytotoxic (cells that can kill target cells bearing appropriate antigens), and they interact with antigen presented on target cells in association with MHC class I molecules. These T cells can inhibit the biologic functions of B cells or other T cells (75). Although the primary biologic role of cytotoxic T cells (CTLs) seems to be lysis of virus-infected autologous cells, cytotoxic immune T cells can mediate the lysis of tumor cells directly. Presumably, CTLs recognize antigens associated with MHC class I molecules on tumor cells through their antigen-specific T-cell receptor, setting off a series of events that ultimately results in the lysis of the target cell.
Monocytes and macrophages, which are myeloid cells, have important roles in both innate and adaptive immune responses; macrophages play a key part in the generation of immune responses. T cells do not respond to foreign antigens unless those antigens are processed and presented by antigen-presenting cells. Macrophages (and B cells and dendritic cells) express MHC class II molecules and are effective antigen-presenting cells for CD4 T cells. Helper-inducer (CD4) T cells that bear a T-cell receptor of appropriate antigen and self-specificity are activated by this antigen-presenting cell to provide help (various factors—lymphokines—that induce the activation of other lymphocytes). In addition to their role as antigen-presenting cells, macrophages play an important part in innate responses by ingesting and killing microorganisms. Activated macrophages, besides their many other functional capabilities, can act as cytotoxic, antitumor killer cells.