Analysis of effector mechanisms against HTLV-I- and HTLV-III/LAV-infected lymphoid cells.
Acquired immunodeficiency syndrome is associated with a viral (HTLV-III/LAV)-mediated progressive depletion of a helper/inducer T4+ T cell subset, whereas acute T cell leukemia is associated with a viral (HTLV-I)-mediated growth of the same T cell subset. Because large granular lymphocytes (LGL) with natural killer (NK) activity have been shown to spontaneously lyse several virus-infected target cells, the ability of NK cells to lyse both HTLV-I- and HTLV-III/LAV-infected lymphoid cell lines and fresh lymphocytes was explored. Normal lymphocytes (T cells and LGL), with and without pretreatment with recombinant interleukin 2 (IL 2), as well as monocytes, with and without pretreatment with interferon-gamma were employed as effectors. Both IL 2-activated T cells and NK cells were cytolytic for HTLV-I-infected targets. However, only LGL demonstrated significant spontaneous activity against HTLV-I-infected targets. Similarly, LGL showed spontaneous cytolytic activity against HTLV-III/LAV-infected targets, and this cytotoxicity was considerably augmented by IL 2. In contrast, T cells and monocytes were unable to lyse HTLV-III/LAV targets, and only minimal activity was induced by activation. LGL cells, B cells, and monocytes were infectible in vitro by high titers of HTLV-III/LAV. However, levels of reverse transcriptase found in these cultures were significantly lower than the levels in T cell cultures. In contrast, only T cells were susceptible to infection by HTLV-I. Experiments with the use of cell cocultures showed that LGL afforded T cells protection from infection by HTLV-I (as indicated by lack of transformation and viral protein expression) but not from infection by HTLV-III/LAV. Collectively, these results indicate that NK cells may play a role in protecting cells against HTLV infection.
Ruscetti
F W
FW
Mikovits
J A
JA
Kalyanaraman
V S
VS
Overton
R
R
Stevenson
H
H
Stromberg
K
K
Herberman
R B
RB
Farrar
W L
WL
Ortaldo
J R
JR
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D017977:Deltaretrovirus / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D012194:RNA-Directed DNA Polymerase / Q000276:immunology; D012191:Retroviridae Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000382:microbiology*; D014779:Virus Replication
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D012191:Retroviridae Proteins; D012194:RNA-Directed DNA Polymerase