Effect of cytokines on HIV-induced depletion of thymocytes in vivo.
BACKGROUND
Cytokines play an important role in the differentiation of thymocytes into mature T cells; consequently, certain cytokines could be useful for immune reconstitution after HIV infection without increasing viral load.


OBJECTIVE
To investigate whether cytokines affect immune depletion caused by HIV infection with a CXCR4-tropic strain in SCID-hu mice implanted with human fetal thymus and liver (thy/liv) tissue.


METHODS
The thy/liv implants were either mock infected or infected with HIV-1 NL4-3, a CXCR4-tropic molecular clone. Interleukin (IL)-2, IL-4, IL-7, interferon-gamma (IFN-gamma) or diluent was administered to the mice during the second and third week postinfection. Viral load and immunophenotype were determined in thymocytes.


RESULTS
Thymocyte subset distributions at 3 weeks postinfection were significantly influenced by treatment with certain cytokines. In particular, IL-2 caused the infected mice to retain a thymocyte profile that was more similar to that in mock-infected mice than that in diluent-treated infected mice, in that the percentages of immature CD4+CD8+ and CD5+CD1+ cells were slightly higher and much less variable than in diluent-treated infected mice. The effect of IFN-gamma treatment was similar to IL-2 but did not reach statistical significance. However, after IFN-gamma treatment, normal percentages of mature CD3+CD69+ cells were maintained whereas this population was relatively increased in diluent-treated infected mice. Although treatment with IL-4 and IL-7 delayed depletion of immature thymocytes, these cytokines increased viral load.


CONCLUSIONS
Cytokines such as IL-2 and IFN-gamma maintain immature thymocytes without increasing viral load and may be useful as adjuncts to improve immune reconstitution after HIV infection.
Department of Pediatrics, the UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, California 90095-1747, USA.
C H
CH
Uittenbogaart
W J
WJ
Boscardin
D J
DJ
Anisman-Posner
P S
PS
Koka
G
G
Bristol
J A
JA
Zack
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D016332:Fetal Tissue Transplantation; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D016130:Immunophenotyping; D016031:Liver Transplantation; D008231:Lymphopenia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000637:transplantation; D014183:Transplantation, Heterologous; D014766:Viremia / Q000188:drug therapy / Q000276:immunology
D016207:Cytokines