Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera.
Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
Hofmann
B
B
Tissue Typing Laboratory, State University Hospital (Rigshospitalet), Copenhagen, Denmark.
Langhoff
E
E
Lindhardt
B O
BO
Odum
N
N
Hyldig-Nielsen
J J
JJ
Ryder
L P
LP
Platz
P
P
Jakobsen
B K
BK
Bendtzen
K
K
Jacobsen
N
N
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D000818:Animals; D002460:Cell Line; D006678:HIV / Q000032:analysis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000032:analysis / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D015728:Receptors, HIV; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011991:Receptors, Virus / Q000502:physiology; D014764:Viral Proteins / Q000494:pharmacology
D007166:Immunosuppressive Agents; D015728:Receptors, HIV; D015375:Receptors, Interleukin-2; D011991:Receptors, Virus; D014764:Viral Proteins