Loss of T cell receptor Vbeta 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) Vbeta repertoire. It is not known if the observed loss of certain Vbeta 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 Vbeta repertoire and the subsequent CD4+ T cell depletion in HIV-1-infected humans. In this study, we examined the human TCR Vbeta 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 Vbeta 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 Vbeta repertoires, reflective of a normal human thymus. However, HIV-1-infected implants in SCID-hu mice had depleted TCR Vbeta repertoires, corresponding with thymocyte depletion. These results indicate that HIV-1-specific mechanisms are the cause of the TCR Vbeta repertoire depletion in infected implants. However, these thymocyte depletions were not restricted to specific TCR Vbeta subsets. These results are not consistent with the hypothesis that HIV-1 acts as a superantigen in vivo. The disruption of the TCR Vbeta 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.
Boldt-Houle
D M
DM
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Jamieson
B D
BD
Aldrovandi
G M
GM
Rinaldo
C R
CR
Ehrlich
G D
GD
Zack
J A
JA
D000818:Animals; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D008212:Lymphocyte Depletion; D051379:Mice; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D018183:Transplantation Chimera
D016693:Receptors, Antigen, T-Cell, alpha-beta