Preservation of lymphocyte immunophenotype and proliferative responses in cryopreserved peripheral blood mononuclear cells from human immunodeficiency virus type 1-infected donors: Implications for multicenter clinical trials

被引:107
作者
Reimann, KA
Chernoff, M
Wilkening, CL
Nickerson, CE
Landay, AL
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA
[2] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA
[3] Rush Presbyterian St Lukes Med Ctr, Dept Clin Immunol & Microbiol, Chicago, IL 60612 USA
[4] Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA
[5] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA
[6] Johns Hopkins Univ, Baltimore, MD 21287 USA
[7] Case Western Reserve Univ, Cleveland, OH 44106 USA
[8] Univ Washington, Seattle, WA 98104 USA
[9] Univ Texas, Med Branch, Galveston, TX 77555 USA
[10] NYU, Med Ctr, New York, NY 10016 USA
关键词
D O I
10.1128/CDLI.7.3.352-359.2000
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human immunodeficiency virus type 1 (HTV-1) infection results in impaired immune function that can be measured by changes in immunophenotypically defined lymphocyte subsets and other in vitro functional assays. These in vitro assays may also serve as early indicators of efficacy when new therapeutic strategies for HIV-1 infection are being evaluated. However, the use of in vitro assays of immune function In multicenter clinical trials has been hindered by their need to be performed on fresh specimens. We assessed the feasibility of using cryopreserved peripheral blood mononuclear cells (PBMC) for lymphocyte immunophenotyping and for lymphocyte proliferation at nine laboratories. In HIV-1-infected patients with moderate CD4(+) lymphocyte loss, the procedures of density gradient isolation, cryopreservation, and thawing of PBMC resulted in significant loss of CD19(+) B cells but no measurable loss of total T cells or CD4(+) or CD8(+) T cells, No significant changes were seen in CD28(-) CD95(+) lymphocytes after cell isolation and cryopreservation. However, small decreases in HLA-DR+ CD38(+) lymphocytes and of CD45RA(+) CD62L(+) were observed within both the CD4(+) and CD8(+) subsets. Fewer than 10% of those specimens that showed positive PBMC proliferative responses to mitogens or microbial antigens lost their responsiveness after cryopreservation. These results support the feasibility of cryopreserving PBMC for immunophenotyping and functional testing in multicenter AIDS clinical trials. However, small changes in selected lymphocyte subsets that may occur after PBMC isolation and cryopreservation will need to be assessed and considered in the design of each clinical trial.
引用
收藏
页码:352 / 359
页数:8
相关论文
共 33 条
[1]   Approximate is better than "exact" for interval estimation of binomial proportions [J].
Agresti, A ;
Coull, BA .
AMERICAN STATISTICIAN, 1998, 52 (02) :119-126
[2]   Improvement in cell-mediated immune function during potent anti-human immunodeficiency virus therapy with ritonavir plus saquinavir [J].
Angel, JB ;
Kumar, A ;
Parato, K ;
Filion, LG ;
Diaz-Mitoma, F ;
Daftarian, P ;
Pham, B ;
Sun, E ;
Leonard, JM ;
Cameron, DW .
JOURNAL OF INFECTIOUS DISEASES, 1998, 177 (04) :898-904
[3]   LYMPHOCYTE SUBSET ANALYSIS BY FLOW-CYTOMETRY - COMPARISON OF 3 DIFFERENT STAINING TECHNIQUES AND EFFECTS OF BLOOD-STORAGE [J].
ASHMORE, LM ;
SHOPP, GM ;
EDWARDS, BS .
JOURNAL OF IMMUNOLOGICAL METHODS, 1989, 118 (02) :209-215
[4]   Positive effects of combined antiretroviral therapy on CD4(+) T cell homeostasis and function in advanced HIV disease [J].
Autran, B ;
Carcelain, G ;
Li, TS ;
Blanc, C ;
Mathez, D ;
Tubiana, R ;
Katlama, C ;
Debre, P ;
Leibowitch, J .
SCIENCE, 1997, 277 (5322) :112-116
[5]   EXPRESSION OF COSTIMULATORY MOLECULE CD28 ON T-CELLS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - FUNCTIONAL AND CLINICAL CORRELATIONS [J].
BRINCHMANN, JE ;
DOBLOUG, JH ;
HEGER, BH ;
HAAHEIM, LL ;
SANNES, M ;
EGELAND, T .
JOURNAL OF INFECTIOUS DISEASES, 1994, 169 (04) :730-738
[6]   GUIDELINE FOR FLOW CYTOMETRIC IMMUNOPHENOTYPING - A REPORT FROM THE NATIONAL-INSTITUTE-OF-ALLERGY-AND-INFECTIOUS-DISEASES, DIVISION OF AIDS [J].
CALVELLI, T ;
DENNY, TN ;
PAXTON, H ;
GELMAN, R ;
KAGAN, J .
CYTOMETRY, 1993, 14 (07) :702-715
[7]   ANALYSIS OF HUMAN ANTIVIRAL CYTOTOXIC T-LYMPHOCYTE RESPONSES FOR VACCINE TRIALS USING CRYOPRESERVED MONONUCLEAR LEUKOCYTES - DEMONSTRATION OF FEASIBILITY WITH INFLUENZA VIRUS-SPECIFIC RESPONSES [J].
ELDAHER, N ;
NICHOLS, JE ;
ROBERTS, NJ .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 1994, 1 (05) :487-492
[8]   Immunologic effects of combined protease inhibitor and reverse transcriptase inhibitor therapy in previously treated chronic HIV-1 infection [J].
Giorgi, JV ;
Majchrowicz, MA ;
Johnson, TD ;
Hultin, P ;
Matud, J ;
Detels, R .
AIDS, 1998, 12 (14) :1833-1844
[9]  
GIORGI JV, 1993, J ACQ IMMUN DEF SYND, V6, P904
[10]   RAPID TURNOVER OF PLASMA VIRIONS AND CD4 LYMPHOCYTES IN HIV-1 INFECTION [J].
HO, DD ;
NEUMANN, AU ;
PERELSON, AS ;
CHEN, W ;
LEONARD, JM ;
MARKOWITZ, M .
NATURE, 1995, 373 (6510) :123-126