Frequency

The number of tetramers available for the study of CD8+ T-cell populations specific for various viruses is increasing [e.g. influenza (26), HIV (19), EBV (27), CMV (28), hepatitis B virus (HBV) (29), hepatitis C virus HCV (30), human papillomavirus (HPV) (31), human T-cell lymphotrophic virus type 1 (HTLV-1) (32), RSV (33) and dengue virus (34)], covering a large range of HLA types. Together with these technological advances, a better identification of individuals in early stages of viral infections have facilitated more detailed studies of virus specific CD8+ T-cells found in human peripheral blood from primary infection to the establishment of viral latency. During primary infection, most viruses induce a substantial antigen-driven activation and expansion of CD8+ T-cells, referred to as the "effector phase" (35). The use of tetramers has revealed that T-cell frequencies in diverse viral infection are much higher than estimated previously. The expansion during the primary infection is such that a population specific for one single viral epitope (from an EBV lytic protein) was shown to reach up to 44% of the total CD8+ T-cells at that moment 27. Responses specific for more than one viral epitope are usually elicited. Subsequently as the viral burden is lowered or cleared, the majority of the CTLs undergo apoptosis, giving place during the "memory phase" to a long lasting pool of resting T-cells, which provide a faster and more effective response to reinfection or virus rebound, upon reactivation and expansion of these cells. The frequency of virus specific CD8+ T-cells detected following primary infection vary according to the virus considered. For instance HIV, EBV and notably CMV seem to induce particularly strong responses; during chronic infection, it is not unusual to detect 1% to 10% CD8+ T-cells specific for these viruses. This phenomenon is most certainly related to continuous antigenic stimulation in the light of persistence of these viruses. In HIV infection, suppression of viral replication using drugs results in a decline of HIV specific T-cell numbers (36). Moreover, T-cell frequencies for viruses that cause limited infection of the host (e.g. influenza) are usually low (<0.1%) after resolution of primary infection (26). There is no consensus as regards a correlation between frequencies of virus specific CD8+ T-cells and viral control. It is certain though that the presence of virus specific CD8+ T-cells per se does not prevent viral spread and the development of virus associated complications in some patients. This has led to hypothesizes of dysfunctional CTL enable to suppress viral replication, for instance due to poor effector functions, anergy or exhaustion, and to direct studies on the functional and phenotypic characteristics of the CD8+ T-cells to verify this hypothesis.

0 0

Post a comment