       Document 0071
 DOCN  M9610071
 TI    Investigations on autologous T-cells for adoptive immunotherapy of AIDS.
 DT    9601
 AU    van Lunzen J; Schmitz J; Dengler K; Kuhlmann C; Schmitz H; Dietrich M;
       Clinical Medicine Section, Bernhard-Nocht-Institute for Tropical;
       Medicine, Hamburg, Germany.
 SO    Adv Exp Med Biol. 1995;374:57-70. Unique Identifier : AIDSLINE
       MED/96047238
 AB    We report on the preclinical results of an immunotherapeutic approach of
       AIDS mediated by ex vivo propagated CD4+ and CD8+ T-cells. A mean yield
       of 6.23 x 10(9) lymphocytes, containing 1.82 x 10(9) CD4+, 3.23 x 10(9)
       CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral blood progenitor
       cells (PBPC) were be obtained by continuous flow cytapheresis (CFC) in
       15 asymptomatic HIV infected patients (CD4-count > 350/mm3). The CD4/CD8
       ratio (mean: 0.53, SD: +/- 0.15) in the cell concentrates reflected the
       distribution of the circulating lymphocyte subsets in vivo. Absolute
       lymphocyte counts decreased at a mean of 404/microliter (25%)
       immediately after CFC but were replaced from the extravascular pool
       within one hour. Neither the CD4/CD8 ratio nor p24-antigen and neopterin
       levels did change significantly after cell separation. No alteration of
       the number of proviral DNA copies (1/10(3)-1/10(6)) could be detected in
       peripheral T-helper cells by semiquantitative PCR after lymphapheresis.
       Cells were cryopreserved in liquid nitrogen without substantial loss of
       viability or function. Ex vivo propagation of T-cells in a strictly
       autologous manner in the presence of PHA + IL-2 for 14d resulted in a
       50-fold expansion rate (140-fold in healthy controls, p < 0.001). Viral
       replication could be controlled but not completely eliminated by
       cocultivation with autologous CD8+ T-lymphocytes as measured by limiting
       dilution nested PCR (NPCR). The expanded cells showed the typical
       phenotype of highly activated memory type T-lymphocytes (CD3+ CD45RO+
       CD25+ HLA-DR+). The distribution of CD4+ and CD8+ T-cells did not reveal
       significant changes before and after culture indicating that both
       subsets were equally expanded. Functionally important membrane or
       intracellular epitopes which were found to be decreased in HIV infected
       subjects (CD7, CD55, CD59) before culture were reconstituted after ex
       vivo propagation of T-cells. The functional importance of the
       up-regulation of complement regulating epitopes (CD55, CD59) after
       culture could be proven by a significant inhibition of cytolysis of
       T-cells in the presence of autologous complement. The majority (75%) of
       expanded CD8+ T-cells stained positive with mAb TIA-1 which is directed
       to intracellular granules within cytotoxic T-cells. Furthermore,
       programmed cell death of expanded T-cells could be prevented by
       cocultivation with fibroblasts which are believed to secrete a cytokine
       pattern preventing activated T-cells from apoptosis after withdrawal of
       IL-2 and other stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Acquired Immunodeficiency Syndrome/*THERAPY  AIDS-Related Opportunistic
       Infections/PREVENTION & CONTROL/  THERAPY  Blood Transfusion, Autologous
       Case-Control Studies  Cell Division  Human  HIV Antibodies/*BIOSYNTHESIS
       HIV-1/PHYSIOLOGY  *Immunotherapy, Adoptive  Leukapheresis  Support,
       Non-U.S. Gov't  *T-Lymphocytes  Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

