Clonal deletion

Hepatocellular carcinoma (HCC) develops in patients with chronic liver diseases associated with hepatitis B and hepatitis C vims infections with high incidences. Here, an acyclic retinoid has been shown to suppress the posttherapeutic recurrence after interferon-y or glycerrhicin treatment in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induced the disappearance of serum lectin-reactive a-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of... 

Clonal deletion. Contact with antigen in the neonate results in death or permanent inactivation of the developing lymphocytes. 

SCT includes autologous and allogeneic transplants and the choice is dependent on the end result desired as well as the risks and benefits of each procedure. Autologous transplants after immunoablative therapy function on the premise of T-cell suppression versus clonal deletion as a cause of tolerance induction in autoimmunity. 

This is explained by the fact that the lymphocytes that respond to antigens during development are eliminated by apoptosis, a process known as clonal deletion. The lymphocytes subsequently present in the foetus will respond only to foreign proteins, for example, those in a graft from another person which then leads to its rejection. Not surprisingly, the system is more complicated than this. The MHC proteins are required to help the lymphocytes differentiate between self and non-self proteins and much of the antigenic difference between individuals lies in the MHC-class II protein. 

N3. Nemazee, D. A., and Biirki, K., Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature 337, 562-566 (1989). 

Tolerance following the intake of a large dose of antigen develops through clonal deletion of specific Thl lymphocytes or increase in the number of antigen nonspecific... 

Administering large doses of antigen leads to a decrease of specific TCR and consequently, reduced release of cytokines characteristic of Thl and Th2 lymphocytes, i.e., IL 2, IFNy, IL 5, and IL 4, as a result of clonal deletion. Among other persisting T CD4 lymphocytes, reduced IL 2 receptor expression and failure to release some cytokines (IL 2, 4, 10, and/or TGFP) is observed. As a result their response to the antigen is weaker (Cohn, 2001). 

Nemazee, D., and Burki, K. (1989). Clonal Deletion of B Lymphocytes in a Transgenic Mouse Bearing Anti-MHC Class I Antibody Genes. Nature 337 562. 

Clonal deletion of self-reactive T- and B-ceUs during development, which removes lymphocytes with high-avidity receptors for ubiquitous self-antigen present in the thymus and marrow. This is known as central tolerance. 

Immunological ignorance. Most self-antigen is presented with insufficient avidity to induce either clonal deletion or lymphocyte activation. Immunological ignorance refers to the... 

Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, Von Andi ian UH (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7 1092—1100. 

The mechanisms most often proposed for tolerance are (i) clonal deletion (elimination of the tolerogen-specific clone) and, (ii) excessive activation of Ts cells. 

Papiernik, M. et al. (1998) Regulatory CD4 T cells expression of IL-2R a chain, resistance to clonal deletion and IL-2 dependency. International Immunology,... 

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