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.