Study of the T cell receptor repertoire in viral immunodeficiency disease.

Abstract

In recent years, descriptive studies of the T cell repertoire have contributed in several ways to our understanding of immunodeficiency disease. In human AIDS, it was shown that, overall, TCR repertoire perturbations of various magnitude were taking place throughout the course of disease in both the CD4+ and CD8+ T cell subsets. Available evidence suggests that the repertoire is remarkably stable within a given individual in absence of serious pathological conditions, even across long periods of time (Ciurli et al., unpublished). The fact that patients with AIDS present with TCR repertoire perturbations, even throughout the so-called clinically silent phase of the disease, testifies to the extent of immune destruction that is taking place covertly within the peripheral lymphoid tissues. Since preferential deletions of CD4+ T cells expressing specific Vβ subsets are not consistently seen, and since no HIV protein has so far fulfilled all the classical characteristics of SAgs, one must argue that there is so far little support for the proposal that HIV encodes a conventional SAg. Preferential replication of HIV-1 in Vβ12+ cells seemed to provide both specificity and functional purpose for such an HIV-encoded SAg. However, it now seems that this superantigenic activity is in fact associated more closely with CMV infection. The fact that HIV uses SAg activity supplied in trans by a co-infecting pathogen is another good example of how lentiviruses and herpesviruses mutually profit from each other's functions to further their individual replicative needs. Whether this Vβ12 reservoir is in fact pathologically relevant still remains to be addressed.