       Document 0109
 DOCN  M9630109
 TI    AKR.H-2b lymphocytes inhibit the secondary in vitro cytotoxic
       T-lymphocyte response of primed responder cells to AKR/gross murine
       leukemia virus-induced tumor cell stimulation.
 DT    9603
 AU    Rich RF; Green WR; Department of Microbiology, Dartmouth Medical School,
       Lebanon,; New Hampshire 03756, USA.
 SO    J Virol. 1996 Jan;70(1):402-14. Unique Identifier : AIDSLINE
       MED/96099456
 AB    We have previously shown that AKR.H-2b congenic mice, though carrying
       the responder H-2b major histocompatibility complex haplotype, are
       unable to generate secondary cytolytic T-lymphocyte (CTL) responses
       specific for AKR/Gross murine leukemia virus (MuLV). Our published work
       has shown that this nonresponsive state is specific and not due to
       clonal deletion or irreversible functional inactivation of antiviral CTL
       precursors. In the present study, an alternative mechanism based on the
       presence of inhibitory AKR.H-2b cells was examined. Irradiated or
       mitomycin C-treated AKR.H-2b spleen cells function as in vitro
       stimulator cells in the generation of C57BL/6 (B6) anti-AKR/Gross virus
       CTL, consistent with their expression of viral antigens. In contrast,
       untreated viable AKR.H-2b spleen cells functioned very poorly as
       stimulators in vitro. Viable AKR.H-2b spleen cells were also able to
       cause dramatic (up to > or = 25-fold) inhibition of antiviral CTL
       responses stimulated in vitro by standard AKR/Gross MuLV-induced tumor
       cells. This inhibition was specific: AKR.H-2b modulator spleen cells did
       not inhibit allogeneic major histocompatibility complex-specific CTL
       production, even when a concurrent antiviral CTL response in the same
       culture well was inhibited by the modulator cells. These results and
       those of experiments in which either semipermeable membranes were used
       to separate AKR.H-2b modulator spleen cells from AKR/Gross MuLV-primed
       responder cells or the direct transfer of supernatants from wells where
       inhibition was demonstrated to wells where there was antiviral CTL
       responsiveness argued against a role for soluble factors as the cause of
       the inhibition. Rather, the inhibition was dependent on direct contact
       of AKR.H-2b cells in a dose-dependent manner with the responder cell
       population. Inhibition was shown not to be due to the ability of
       AKR.H-2b cells to function as unlabeled competitive target cells.
       Exogenous interleukin-2 added at the onset of the in vitro
       CTL-generating cultures partially restored the antiviral response that
       was decreased by AKR.H-2b spleen cells. Positive and negative cell
       selection studies and the development of inhibitory cell lines indicated
       that B lymphocytes and both CD4- CD8+ and CD4+ CD8- T lymphocytes from
       AKR.H-2b mice could inhibit the generation of AKR/Gross virus-specific
       CTL in vitro. AKR.H-2b macrophages were shown not to be required to
       demonstrate AKR/Gross MuLV-specific inhibition, however, confirming that
       the inhibition by T-cell (or B-cell)-depleted spleen populations was
       dependent on the enriched B-cell (T-cell) population per se.(ABSTRACT
       TRUNCATED AT 250 WORDS)
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  AKR Virus/*IMMUNOLOGY
       B-Lymphocytes/IMMUNOLOGY/METABOLISM  Cell Survival  Cells, Cultured
       CD4-Positive T-Lymphocytes/IMMUNOLOGY/METABOLISM  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY/METABOLISM  Female  H-2 Antigens
       Interleukin-2/PHARMACOLOGY  Male  Mice  Mice, Inbred AKR  Mice, Inbred
       C57BL  Mitomycin C/PHARMACOLOGY  Spleen/CYTOLOGY/DRUG EFFECTS/RADIATION
       EFFECTS  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes, Cytotoxic/*IMMUNOLOGY/METABOLISM  Tumor Cells, Cultured
       JOURNAL ARTICLE

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

