Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens

Hong Nerng Ho, Lance E. Hultin, Ronald T. Mitsuyasu, Jose L. Matud, Mary Ann Hausner, David Bockstoce, Chen Cheng Chou, Sheryl O'Rourke, Jeremy M G Taylor, Janis V. Giorgi

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Abstract

CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 ± 132/mm3) and AIDS patients (253 ± 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 ± 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cell numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.

Original languageEnglish
Pages (from-to)3070-3079
Number of pages10
JournalJournal of Immunology
Volume150
Issue number7
Publication statusPublished - Dec 1 1993
Externally publishedYes

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Immunologic Cytotoxicity
pol Gene Products
env Gene Products
Antibody Binding Sites
CD8 Antigens
gag Gene Products
Immunophenotyping
Competitive Binding
Differentiation Antigens
Cytotoxic T-Lymphocytes
HLA-DR Antigens
HIV Infections
HIV
T-Lymphocytes
gag-pol Fusion Proteins
Acquired Immunodeficiency Syndrome
Lymphocytes
pol Genes
gag Genes
env Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Ho, H. N., Hultin, L. E., Mitsuyasu, R. T., Matud, J. L., Hausner, M. A., Bockstoce, D., ... Giorgi, J. V. (1993). Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens. Journal of Immunology, 150(7), 3070-3079.

Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens. / Ho, Hong Nerng; Hultin, Lance E.; Mitsuyasu, Ronald T.; Matud, Jose L.; Hausner, Mary Ann; Bockstoce, David; Chou, Chen Cheng; O'Rourke, Sheryl; Taylor, Jeremy M G; Giorgi, Janis V.

In: Journal of Immunology, Vol. 150, No. 7, 01.12.1993, p. 3070-3079.

Research output: Contribution to journalArticle

Ho, HN, Hultin, LE, Mitsuyasu, RT, Matud, JL, Hausner, MA, Bockstoce, D, Chou, CC, O'Rourke, S, Taylor, JMG & Giorgi, JV 1993, 'Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens', Journal of Immunology, vol. 150, no. 7, pp. 3070-3079.
Ho HN, Hultin LE, Mitsuyasu RT, Matud JL, Hausner MA, Bockstoce D et al. Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens. Journal of Immunology. 1993 Dec 1;150(7):3070-3079.
Ho, Hong Nerng ; Hultin, Lance E. ; Mitsuyasu, Ronald T. ; Matud, Jose L. ; Hausner, Mary Ann ; Bockstoce, David ; Chou, Chen Cheng ; O'Rourke, Sheryl ; Taylor, Jeremy M G ; Giorgi, Janis V. / Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens. In: Journal of Immunology. 1993 ; Vol. 150, No. 7. pp. 3070-3079.
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N2 - CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 ± 132/mm3) and AIDS patients (253 ± 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 ± 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cell numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects.

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