Differential tropism of HIV-1 isolates for distinct thymocyte subsets in vitro.
OBJECTIVE
Understanding the interaction between HIV and developing thymocytes is crucial in determining how HIV infection perturbs the immune system. We determined which thymocyte subsets can harbor and express HIV.


METHODS
HIV expression in mature and immature thymocytes obtained from surgical specimens from non-infected children was determined after in vitro infection with the syncytium-inducing, cytopathic NL4-3 and the non-syncytium-inducing, relatively noncytopathic JR-CSF isolates.


METHODS
Intracellular staining for the HIV p24gag antigen was combined with cell surface phenotyping to determine thymocyte subsets expressing HIV. Infection was quantitated by polymerase chain reaction on sorted subsets.


RESULTS
NL4-3 replicated faster and to higher titers and caused a more severe decrease of all CD4-bearing thymocytes than did JR-CSF. In addition, both immature CD1+ and mature CD1-thymocytes expressed NL4-3, whereas only mature CD1-cells expressed JR-CSF. The tropism of NL4-3 for these immature cells suggests a mechanism for a more profound impact on T-cell maturation than that seen with JR-CSF. We also found that thymocytes lacking cell surface CD4 (CD4-CD8- and CD4-CD8+ subsets) expressed virus with either isolate late in infection, when viral levels were high. The CD4-CD8- cells expressing HIV were mature CD3bright T-cell receptor (TCR) alpha/beta bright cells.


CONCLUSIONS
These results show that NL4-3 can be expressed by thymocytes at immature and mature stages of differentiation and cause severe loss of CD4+ cells. Thus, tropism of a virus for immature cells can affect the capability of the thymus to produce new T lymphocytes leading to a greater impact on development and functions of the immune system. It is proposed that this in vitro model can be used to study pathogenic mechanisms in the thymus.
Uittenbogaart
C H
CH
Department of Pediatrics, University of California Los Angeles School of Medicine, USA.
Anisman
D J
DJ
Jamieson
B D
BD
Kitchen
S
S
Schmid
I
I
Zack
J A
JA
Hays
E F
EF
D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000276:immunology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000821:virology; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000821:virology; D013601:T-Lymphocytes / Q000821:virology*; D018523:Tropism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D004279:DNA, Viral; D016655:HIV Core Protein p24; D007376:Interleukin-2; D015851:Interleukin-7; D011994:Recombinant Proteins; D015847:Interleukin-4