title: Loss of CD4+ T cell proliferative ability but not loss of human immunodeficiency virus type 1 specificity equates with progression to disease.
abstract: In this study, we compared human immunodeficiency virus (HIV) type 1-specific proliferative responses with HIV-1-induced intracellular cytokine production in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1-specific proliferative responses in the clinical nonprogressor cohort that correlated with significant numbers of circulating HIV-1-specific CD4(+) T cells. In contrast, HIV-1-specific proliferative responses were absent in most individuals with progressive HIV-1 infection, even though interferon-gamma-producing HIV-1-specific CD4(+) T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive patients from very early in disease may be an inability of HIV-1-specific CD4(+) memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus-specific CD4(+) T cells.
authors.affiliation: Nature Immunology, New York City, NY, USA. jdkwilson@hotmail.com.
authors.forename: J D
authors.initials: JD
authors.lastname: Wilson
authors.forename: N
authors.initials: N
authors.lastname: Imami
authors.forename: A
authors.initials: A
authors.lastname: Watkins
authors.forename: J
authors.initials: J
authors.lastname: Gill
authors.forename: P
authors.initials: P
authors.lastname: Hay
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: M
authors.initials: M
authors.lastname: Westby
authors.forename: F M
authors.initials: FM
authors.lastname: Gotch
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology* / Q000821:virology; D002455:Cell Division; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005434:Flow Cytometry; D015658:HIV Infections / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D019562:Viral Load
chemical_list: D000956:Antigens, Viral; D016207:Cytokines