Infection of T cell subsets by HIV-1 and the effects of interleukin-12.
CD4+ lymphocytes constitute one of the major cell targets for human immunodeficiency virus type 1 (HIV-1) infection. The eventual loss of CD4+ lymphocytes contributes substantially to the pathogenesis of HIV-1 and development of acquired immunodeficiency syndrome (AIDS). CD4+ lymphocytes consist of the subgroups Th1, Th2, and Th0, which differ in their cytokine profile. Th1 cells produce cytokines that favor cell-mediated immune responses, whereas Th2 cells produce cytokines that favor humoral immunity. Th0 cells are precursors to the Th1 and Th2 subsets. A shift from a Th1 to a Th2 response has been reported for HIV-1-infected patients (Kannagi et al. 1990. J. Virol. 64, 3399-3406; Walker et al. 1986. Science 234, 1563-1566; Walker et al. 1991. J. Virol. 65, 5921-5927). For this reason, the potential role of cytokines in the development of AIDS has received a great deal of attention. Interleukin (IL)-12 is a disulfide-linked, 70-kDa heterodimeric cytokine produced by antigen-presenting cells. IL-12 has a central role in the development of the Th1-type immune responses. Therefore, we investigated the ability of T-tropic HIV-1 IIIB to replicate in Th1, Th2, and Th0 T cell clones and studied the effects of IL-12 on HIV-1 replication in these cells types. These studies demonstrate several points. (1) Th1, Th2, and Th0 T cell clones support HIV-1 IIIB replication nearly equally well, and it is, therefore, unlikely that differences in ability to support HIV-1 replication can explain changes in Th1, Th2, or Th0 subtype 1 following HIV-1 infection. (2) Using this model, we show that IL-12 can inhibit HIV-1 replication, consistent with a role for IL-12 in HIV-1 replication in T cells. (3) HIV-1 can form a persistent infection in T cell clones, providing a reservoir model for study of viral sanctuary and persistence in a system closely approximating the in vivo situation.
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA. salgame@astro.ocis.temple.edu
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Salgame
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Guan
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Agahtehrani
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Henderson
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D002460:Cell Line; D000939:Epitopes; D015497:HIV-1; D006801:Humans; D018664:Interleukin-12 / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000821:virology*; D018417:Th1 Cells / Q000821:virology; D018418:Th2 Cells / Q000821:virology; D014779:Virus Replication
D000939:Epitopes; D018664:Interleukin-12