TY - JOUR
T1 - Limiting dilution analysis of in vivo-activated (IL-2 responsive) peripheral blood lymphocytes in HIV-1-infected subjects
AU - Donnenberg, Albert D.
AU - Margolick, Joseph B.
AU - Polk, B. Frank
N1 - Funding Information:
i This work was supported by contract DAMD 17-88-C-8929 from the U.S. Army and BRSG Grant 12-86 from Johns Hopkins University. Dr. Donnenberg is the recipient of a Carter-Wallace Fellowship. * Dr. B. Frank Polk died on October 11, 1988. This article is dedicated to his memory.
PY - 1989/4
Y1 - 1989/4
N2 - The progression of infection with human immunodeficiency virus, type 1 (HIV-1), is associated with a loss of helper T cell function, but the mechanism for this loss (e.g., decreased absolute number of helper cells, altered function of helper cells, or both) has not been delineated. Many studies have suggested that T-cell production of and/or responsiveness to the T cell growth factor interleukin-2 (IL-2) declines over the course of HIV-1 infection. Using a highly quantitative 6-day limiting dilution assay (LDA), we investigated whether the number and the proliferative capacity of circulating IL-2 responsive cells in patients with AIDS differ from those in patients in earlier stages of HIV-1 infection (asymptomatic or AIDS-related complex) and healthy seronegative individuals. The frequency of IL-2 responsive cells declined progressively in asymptomatic seropositive subjects, those with ARC, and those with AIDS. In contrast, the proliferative capacity of individual IL-2 responsive cells, as reflected by the magnitude of thymidine uptake per precursor, was reduced only in patients with frank AIDS and was normal in asymptomatic subjects and in those with ARC. These results suggest that the development of AIDS in the setting of HIV-1 infection may reflect a combination of qualitative as well as quantitative changes in lymphocyte function. They also suggest that analysis of lymphocyte responsiveness to IL-2 may provide a useful approach to prediction of the development of AIDS in individuals infected with HIV-1.
AB - The progression of infection with human immunodeficiency virus, type 1 (HIV-1), is associated with a loss of helper T cell function, but the mechanism for this loss (e.g., decreased absolute number of helper cells, altered function of helper cells, or both) has not been delineated. Many studies have suggested that T-cell production of and/or responsiveness to the T cell growth factor interleukin-2 (IL-2) declines over the course of HIV-1 infection. Using a highly quantitative 6-day limiting dilution assay (LDA), we investigated whether the number and the proliferative capacity of circulating IL-2 responsive cells in patients with AIDS differ from those in patients in earlier stages of HIV-1 infection (asymptomatic or AIDS-related complex) and healthy seronegative individuals. The frequency of IL-2 responsive cells declined progressively in asymptomatic seropositive subjects, those with ARC, and those with AIDS. In contrast, the proliferative capacity of individual IL-2 responsive cells, as reflected by the magnitude of thymidine uptake per precursor, was reduced only in patients with frank AIDS and was normal in asymptomatic subjects and in those with ARC. These results suggest that the development of AIDS in the setting of HIV-1 infection may reflect a combination of qualitative as well as quantitative changes in lymphocyte function. They also suggest that analysis of lymphocyte responsiveness to IL-2 may provide a useful approach to prediction of the development of AIDS in individuals infected with HIV-1.
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U2 - 10.1016/0090-1229(89)90209-2
DO - 10.1016/0090-1229(89)90209-2
M3 - Article
C2 - 2784365
AN - SCOPUS:0024583962
SN - 0090-1229
VL - 51
SP - 91
EP - 98
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 1
ER -