CD8+ T lymphocytes of African green monkeys secrete an immunodeficiency virus-suppressing lymphokine.
Following natural and experimental infection by simian immunodeficiency virus SIVagm of African green monkeys (AGMs), the natural host, there is no evidence for the development of an immunodeficiency. Within the framework of our studies on human immunodeficiency virus (HIV)/SIV pathogenesis, we investigated the influence of CD8 T lymphocytes on SIVagm replication in AGM CD4 T lymphocytes in vitro. The following observations were made: (i) Peripheral blood mononuclear cells from both seronegative and seropositive AGMs contained only a low proportion (i.e., 10%) of CD4+ lymphocytes, whereas a high proportion (80%) of CD8+ cells was detected. Even after persistent SIVagm infection, CD4 T lymphocytes do not decrease in number. (ii) The target of in vitro infection of peripheral blood cells is the CD4+ mononuclear cell (T lymphocytes, monocytes) and SIVagm infects by binding to the CD4 molecule. (iii) In both naturally and experimentally SIVagm-infected AGMs the CD4+ T cells and monocytes, but not the CD8+ T cells, harbor DNA provirus. (iv) Virus reisolation and virus replication of SIVagm in CD4 T lymphocytes from seropositive AGMs is suppressed in the presence of autologous CD8 T lymphocytes or a soluble factor produced by these cells. Taken together, one possible reason for the apathogenicity of the SIVagm infection in AGMs may be the suppression of virus replication by a soluble, yet unidentified factor secreted by CD8 lymphocytes quantitatively dominating among peripheral blood cell populations. We have tentatively termed this factor "immunodeficiency virus-suppressing lymphokine." In addition, we show that immunodeficiency virus-suppressing lymphokine from AGMs is able to suppress HIV-1 replication in human CD4+ T cells.
Ennen
J
J
Paul-Ehrlich Institute, Langen, Germany.
Findeklee
H
H
Dittmar
M T
MT
Norley
S
S
Ernst
M
M
Kurth
R
R
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D016827:CD8 Antigens; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000032:analysis; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000382:microbiology; D011533:Proviruses / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D014779:Virus Replication
D016827:CD8 Antigens; D004279:DNA, Viral; D008222:Lymphokines