title: Analysis of CD8+ T lymphocyte-mediated nonlytic suppression of autologous and heterologous primary human immunodeficiency virus type 1 isolates.
abstract: Nonlytic CD8+ T lymphocyte antiviral factor (CAF) activity has been described as having an important role in the clinical course of human immunodeficiency virus type 1 (HIV-1) infection. Testing of CAF activity against autologous viruses isolated at approximately the same time points showed that CD8+ T lymphocytes from long-term survivors indeed possessed high CAF activity. However, in four of six progressors to AIDS, we observed the same amount of CAF activity in the face of increasing cellular HIV-1 load. In the other two progressors, CAF activity seemed preserved over time whereas the susceptibility of the virus isolate obtained late in infection seemed to be diminished. In a heterologous system, CAF activity of CD8+ T lymphocytes from 13 HIV-1-positive individuals did not correlate with CD4+ T lymphocyte counts. In two of three patients, syncytium-inducing (SI) HIV-1 variants, which are associated with a progressive clinical course, appeared to have a somewhat reduced susceptibility to CAF activity as compared to their coexisting non-SI HIV-1 variants. In a large donor group, suppression of SI isolates (as compared to non-SI isolates) mediated by heterologous CD8+ T lymphocytes was reduced. CD8+ T lymphocytes from five of six HIV-1-positive individuals suppressed HIV-1 replication in macrophages. CD8+ T lymphocytes from noninfected donors, even from cord blood, already had high CAF activity, suggesting that induction of this activity is neither virus nor HIV-1 specific.
authors.affiliation: Department of Clinical Viro-Immunology, The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
authors.forename: N A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood; D015497:HIV-1 / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008297:Male; D014779:Virus Replication / Q000502:physiology*
chemical_list: D019380:Anti-HIV Agents