Loss of T cell receptor VP repertoires in HIV type 1-infected SCID-hu mice

Late-stage HIV-1 disease in humans has been associated with perturbations of the T cell receptor (TCR) V beta repertoire. It is not known if the observed loss of certain V beta families is attributable directly to HIV-1 infection or whether this is a consequence of multiple opportunistic infections, Putative HIV-1-associated superantigens have been postulated to be the cause of the perturbed TCR V beta repertoire and the subsequent CD4(+) T cell depletion in HIV-1-infected humans, In this study, we examined the human TCR V beta repertoire in SCID-hu mice, housed in a pathogen-free environment and infected with a molecularly cloned virus strain, to ascertain directly the effect of HIV-1 on the human TCR V beta repertoire in the absence of other infectious agents, We demonstrate that mock-infected human thymus/liver (Thy/Liv) implants in SCID-hu mice have complete TCR V beta repertoires, reflective of a normal human thymus, However, HIV-1-infected implants in SCID-hu mice had depleted TCR V beta repertoires, corresponding with thymocyte depletion, These results indicate that HIV-1-specific mechanisms are the cause of the TCR V beta repertoire depletion in infected implants, However, these thymocyte depletions were not restricted to specific TCR V beta subsets, These results are not consistent with the hypothesis that HIV-1 acts as a superantigen in vivo, The disruption of the TCR V beta repertoire in the human Thy/Liv implants of the SCID-hu mice suggests that HIV-1 infection may be influencing T cell development in the thymus, contributing to both the overall CD4(+) T cell depletion in AIDS and limited TCR repertoire diversity.