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+ and CD161+ Thymocytes Express HIV-1 in the SCID-hu Mouse, Potentially Contributing to Immune Dysfunction in HIV Infection1
,
,
Departments of
* Microbiology, Immunology, and Molecular Genetics and
Pediatrics,
Jonnson Comprehensive Cancer Center,
University of California, Los Angeles AIDS Institute, and
¶ Division of Infectious Diseases, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095; and
|| Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115
The vast diversity of the T cell repertoire renders the adaptive
immune response capable of recognizing a broad spectrum of potential
antigenic peptides. However, certain T cell rearrangements are
conserved for recognition of specific pathogens, as is the case for
TCR
cells. In addition, an immunoregulatory class of T cells
expressing the NK receptor protein 1A (CD161) responds to nonpeptide
Ags presented on the MHC-like CD1d molecule. The effect of HIV-1
infection on these specialized T cells in the thymus was studied using
the SCID-hu mouse model. We were able to identify CD161-expressing
CD3+ cells but not the CD1d-restricted invariant
V
24/V
11/CD161+ NK T cells in the thymus. A subset of
TCR cells and CD161-expressing thymocytes express CD4, CXCR4, and
CCR5 during development in the thymus and are susceptible to HIV-1
infection. TCR thymocytes were productively infectable by both X4
and R5 virus, and thymic HIV-1 infection induced depletion of
CD4+ TCR cells. Similarly,
CD4+CD161+ thymocytes were depleted by thymic
HIV-1 infection, leading to enrichment of
CD4-CD161+ thymocytes. Furthermore, compared
with the general CD4-negative thymocyte population,
CD4-CD161+ NK T thymocytes exhibited as much
as a 27-fold lower frequency of virus-expressing cells. We conclude
that HIV-1 infection and/or disruption of cells important in both
innate and acquired immunity may contribute to the overall immune
dysfunction seen in HIV-1 disease.
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