CD4‏ and CD8‏ memory T cells undergo phenotypic

 CD4‏ and CD8‏ memory T cells undergo phenotypic

CD4‏ and CD8‏ memory T cells undergo phenotypic changes when under replicative stress. The most widely acknowledged phenotypic change is a loss of CD28, which is increasingly seen in the CD8‏ T-cell population with advancing age and also in CD4‏ T cells to a lesser degree (Posnett et al., 1994; Effros et al., 1994; Effros, 1997). CD4‏CD282 and CD8‏CD282 T cells have also been reported in several chronic infections and few chronic inflammatory diseases, consistent with the view that they represent senescent cells (Choremi-Papadopoulou et al., 1994; Moosig et al., 1998; Markovic-Plese et al., 2001). These cells have shorter telomeres than their CD28‏ counterparts (Monteiro et al., 1996; Batliwalla et al., 1996) CD4‏ CD28- and, in some regards, CD8‏ CD28- T cells are resistant to apoptosis, and they have delayed cell-cycle progression (Spaulding et al., 1999; Vallejo et al., 2000).

The mechanism of CD28 loss in these cells has become increasingly clear in the last years (Vallejo et al., 1998, 1999, 2001, 2002). We have documented that CD28 loss correlates with the loss of a CD28-specific initiator complex that includes the nuclear proteins, nucleolin and hnRNP-D. However, CD28 loss is not the only and is possibly not the most prominent change in gene expression in senescent T cells. Senescent CD4‏ and CD8‏ T cells acquire the expression of many genes that are generally found on natural killer cells (Lanier, 1998; Moretta et al., 2000; Anfossi et al., 2001; Raulet et al., 2001; Young and Uhrberg, 2002). Accumulation of senescent cells in the T-cell pool as the host ages leads to marked changes in functional competence. An interesting question is how this process affects T-cell tolerance. T-cell tolerance is acquired, not inherited, and its induction and maintenance require functional competence of the immune system and all of its cellular components. Therefore, it is not unexpected that self tolerance fails as the system ages.   

        In human cells, the mechanism that controls the process of senescence is believed to be telomere shortening (11, 48). Due to the end-replication problem, normal somatic cells undergo progressive telomere shortening with cell division, and it is the critically short telomere that signals DNA damage and cellcycle arrest.  

    The telomere is a DNA protein complex that is essential for the stabilization of chromosomes. The telomere DNA, located at the end of chromosomes, is not replicated by the usual DNA polymerase, and shortens at each cell division. Telomerase is a reverse transcriptase that adds telomere repeat sequences to the end of chromosomes to maintain telomere structure. Most cancer cells show telomerase activation, resulting in the maintenance of telomere length despite cell division. Telomerase activation also occurs in non-diseased cells including lymphocytes  

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 Dr.Nada Fathy