Effect of cytokines on HIV-induced depletion of thymocytes in vivo

Background: Cytokines play an important role in the differentiation of thym ocytes into mature T cells; consequently, certain cytokines could be useful for immune reconstitution after HIV infection without increasing viral loa d. 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 HI V-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 durin g the second and third week postinfection. Viral load and immunophenotype w ere determined in thymocytes. Results: Thymocyte subset distributions at 3 weeks postinfection were signi ficantly influenced by treatment with certain cytokines. In particular, IL- 2 caused the infected mice to retain a thymocyte profile that was more simi lar to that in mock-infected mice than that in diluent-treated infected mic e, in that the percentages of immature CD4(+)CD8(+) and CD5(+)CD1(+) cells were slightly higher and much less variable than in diluent-treated infecte d mice. The effect of IFN-gamma treatment was similar to IL-2 but did not r each statistical significance. However, after IFN-gamma treatment, normal p ercentages of mature CD3(+)CD69(+) cells were maintained whereas this popul ation was relatively increased in diluent-treated infected mice. Although t reatment 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 thymocy tes without increasing viral load and may be useful as adjuncts to improve immune reconstitution after HIV infection. (C) 2000 Lippincott Williams & W ilkins.