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.
Uittenbogaart
C H
CH
Department of Pediatrics, the UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, California 90095-1747, USA.
Boscardin
W J
WJ
Anisman-Posner
D J
DJ
Koka
P S
PS
Bristol
G
G
Zack
J A
JA
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