Cytotoxic T lymphocytes, or T cytotoxic (Tc) cells, are effector cells found in the peripheral blood that are capable of directly destroying virally infected target cells. Most Tc cells are CD8+ and recognize antigen on the target cell surface associated with MHC class I molecules (e.g., human leukocyte antigen [HLA] types A, B, and C) or MHC class I alone. This process is demonstrated by the immune response to virus-infected cells or tumor cells (Fig. 1).

Fig1. A, Transmission electron  photomicrograph demonstrating the initial stages of the attack of a cytotoxic lymphocyte on a tumor cell, only a portion of  which is seen. Note vesicles and blebs of  cytoplasm being shed by the lymphocyte.  B, Effects of cytotoxic lymphocytes on  tumor cells. 1, Tumor cells before contact  with immune lymphocytes. 2, Tumor cells  after contact. Note that many cells have  detached from the surface, some cells  are swollen, and a few cells exhibit the  morphology of normal cells. (From Barrett JT: Textbook of immunology, ed 5, St Louis, 1988, Mosby.)

In a primary viral infection, naïve CD8+ T cells are primed in secondary lymph nodes and consequently proliferate and differentiate into effector CD8+ T cells to eliminate virus infected cells. After clearance of the virus, most effector CD8+ T cells contract because of apoptosis but a small number of these CD8+ T cells form a memory T cell pool.

Studies have demonstrated that human CD8+ T cells undergo a change in the expression of costimulatory molecules (e.g., CD27, CD28, and CD45RA) on their surface, according to their differentiation and maturation. Cytolytic effector molecules, perforin, and granzyme A-B, are considered to be markers for effector CD8+ T cells because they are the actual functional molecules for killing target cells.

Naïve and central memory CD8+ T cells express the mem brane marker, CCR7, for homing to secondary lymph nodes, but effector memory and effector CD8+ T cells express the chemokine receptors for inflammatory cytokines, which enable the cells to migrate toward infected and inflamed sites. A unique subset of the effector CD8+ T cell population expresses CXCR1. These CXCR1 CD8+ T cells possess chemotactic activity toward the CDCR1 ligand IL-8, a potent inflammatory cytokine produced in inflamed tissues and in tissues infected with some viruses, such as human cytomegalovirus (HCMV) or influenza A. This suggests that these CXCR1+ effector CD8+ T cells immediately migrate to inflamed and infected sites to exert their effector function in the initial stage of an immune response. It is possible that effector CD8+ T cell subsets are functionally distinct populations of T lymphocytes.

In addition to destruction of virally infected, MHC class I–bearing targets, Tc cells are major effectors in allograft organ rejection. Tc cells express CD4 or CD8, depending on the MHC antigen restriction that governs their antigen recognition (i.e., class I or II antigens; Fig. 2).

Fig2. Induction of CD8+ T cell responses against tumors.  Responses to tumors may be induced by cross-priming (or cross-  presentation), in which the tumor cells and tumor antigens are taken up by specialized (so-called professional) APCs, processed, and presented  to T cells. In some cases, B7 costimulators expressed by the APCs provide the second signals for the differentiation of the CD8+ T cells. APCs may  also stimulate CD4+ helper T cells, which provide the second signals for cytotoxic T lymphocyte (CTL) development. Differentiated CTLs kill tumor  cells without a requirement for costimulation or T cell assistance. (From Abbas AK, Lichtman AH: Basic immunology: functions and disorders of the immune system, ed 3, Philadelphia, 2008, Saunders.)

Suppressor T lymphocytes, or T suppressor (Ts) cells, are functionally defined T cells that downregulate the actions of other T and B cells. Ts cells have no unique markers. Although antigen-specific suppression was described in 1970, and many investigators believe that Ts cells are critical in various phases of immunoregulation, peripheral tolerance, and autoimmunity, their mode of action is unclear. Many Ts cells are CD8+ and may operate through secretion of free TCRs.

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مواضيع ذات صلة

Antigen Recognition by T Cells

Antigen Processing and Antigen Presentation to T Cells

T Regulatory Lymphocytes

Helper T Lymphocytes

Sites of Lymphocyte Development

MONOCYTE-MACROPHAGE DISORDERS

Clinical Features of HIV Infection and AIDS

Pathogenesis of AIDS

Congenital Immunodeficiencies : Defects in Lymphocyte Activation and Function

Congenital Immunodeficiencies: Defects in Lymphocyte Maturation

Congenital Immunodeficiencies: Defects in Innate Immunity

Congenital (Primary) Immunodeficiencies