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8th Conference on Retroviruses and Opportunistic InfectionsChicago, IL - February 4 - 8, 2001 |
Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:43 (abstract no. 2)
RW, Price1, J. Neuenburg1,2, A. Nilsson1, R. Pearce1, R. M. Grant1,2, S. Hebert1, J. M. McCune1,2, and E. Sinclair1
1Univ. of California, San Francisco and 2J. D. Gladstone Inst. of Virology & Immunology, San Francisco, CA
BACKGROUND: The cerebrospinal fluid (CSF) space can be a site of 'compartmentalized' HIV infection with respect to both virus and lymphocyte traffic. This study was undertaken to assess expression of activation markers on T cells in CSF compared to blood in HIV infection, and to compare this expression to that in HIV-uninfected controls.
METHODS: A descriptive, cross-sectional survey of a convenience sample undergoing study lumbar punctures. Lymphocytes concentrated from 8-12 ml of CSF were analyzed by 4-color flow cytometry, gating for CD4 and CD8 and measuring frequencies of lymphocytes expressing longer- and shorter-term activation markers: HLA-DR & CD38 and CD69 & CD25.
RESULTS: Analysis at single time points of 31 HIV+ subjects and 11 HIV- controls showed that HLA-DR and CD38 frequencies were generally similar in paired CSF and blood from the HIV+ subjects except for differences between CD38+ CD4+ cells in CSF (median 36.9% ,IQR 20.5-48.3) and blood (45.6%, 37.6-53.4) (p=0.004, uncorrected paired t-test) and between CD4+ cells expressing neither HLA-DR nor CD38 (CSF 60.4%, 39.8-74.4; blood 43.5%, 34.2-54.9) (p=0.000). Both CSF and blood from the HIV+ subjects exhibited higher expression of these markers than HIV- normals (p<0.001, Mann-Whitney). Most striking in the HIV+ group was the difference in CD69 expression between CSF (18.9%, 11.0-34.6) and blood (0.3%, 0.0-0.5) (p<0.000). Moreover, these proportions were similar in the non-HIV- infected subjects (22.6%, 19.5-30.5 and 0.3%, 0.2-0.6).
CONCLUSIONS: The marked increase in CD69 expression on CSF CD4+ cells compared to blood is consistent with the hypothesis that CD4+ lymphocyte activation precedes (and likely is required for) traffic into the CSF, though activation after entry is also possible. Similarity between HIV+ and HIV- subjects may favor activation before entry in showing that reaction to HIV in the CSF is not required for the high-level CD69 expression. These findings also suggest that the mechanisms governing lymphocyte traffic in HIV infection are similar to those occurring in 'normals,' though in the context of a higher background of longer-term lymphocyte activation.
2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.