Most CD4+ T cells from human immunodeficiency virus-1 infected patients can undergo prolonged clonal expansion.
We have addressed the capacity of HIV-1 infection to alter the growth of primary CD4+ T cells, but at the clonal level. Single T cells were expanded in the presence of PHA, IL-2, and small numbers of accessory dendritic cells. We report two new findings. First, T cells from seropositive individuals, even those with AIDS and markedly reduced CD4+ counts, exhibit a normal cloning efficiency, and proliferative capacity. This result is in contrast to two prior reports of a low cloning efficiency in CD4+ T cells from HIV-1-infected patients. Second, when we added high doses of exogenous HIV-1 to T cell clones from control subjects, we observed infection but not cytotoxicity or loss of CD4+ cells, following addition of virus stocks at days 0, 3, and/or 7 of clonal growth. The same HIV-1 isolates markedly reduced CD4+ T cells in bulk mononuclear cultures. When tested at day 11, HIV-1 mRNA was expressed in some cells of exogenously infected clones by in situ hybridization; when tested at day 18, several clones could transactivate a TAT-sensitive cell line. These findings suggest that the loss of CD4+ T cells in infected individuals is not the inevitable result of the activation of latent infection, or spread of a productive infection, during clonal growth.
Langhoff
E
E
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
McElrath
J
J
Bos
H J
HJ
Pruett
J
J
Granelli-Piperno
A
A
Cohn
Z A
ZA
Steinman
R M
RM
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D016827:CD8 Antigens; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D003713:Dendritic Cells / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008297:Male; D009693:Nucleic Acid Hybridization; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D012367:RNA, Viral