Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
CHARACTERIZATION OF IN VITRO GENERATED HLA-DR RESTRICTED CYTOMEGALOVIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES
Diss Abstr Int (Sci); 47(10):4057 1987. Unique Identifier : AIDSLINE ICDB/87638585 Lindsley MD; University of Pittsburgh
Abstract:
Mononuclear leukocytes from 14 cytomegalovirus (CMV)-seropositive and 6 CMV-seronegative normal healthy donors were treated with soluble CMV antigen for 5 days to generate cytotoxic T-lymphocyte (CTL) activity. CMV-antigen stimulated lymphocytes from CMV-seropositive but not CMV-seronegative donors lysed autologous peripheral blood monocyte targets infected with CMV in 13 of 14 donors assayed (mean % virus-specific lysis = 19.0 +/- 4.5%, effector to target ratio of 50:1). Freshly donated, unstimulated lymphocytes displayed little or no lysis of CMV-infected monocytes. Lysis was virus specific in that CMV-stimulated CTL did not kill herpes simplex virus-infected monocytes. HLA-mismatched targets were rarely lysed by anti-CMV CTL. The mean level of lysis of CMV-infected autologous targets was equivalent to that of HLA-DR-matched targets (20.0 +/- 8.0%), and was significantly greater than that of HLA-A/B-matched targets (6.3 +/- 2.5%, p less than 0.035) and HLA-mismatched targets (3.3 +/- 2.5%, p less than 0.01). Enrichment for T-cell subsets using selective depletion methods with monoclonal antibodies showed that CTL activity against autologous and HLA-DR matched allogeneic targets was present predominantly in Leu-3 positive T-lymphocytes. These results show for the first time that short term stimulation of heterogeneous lymphocytes from CMV-seropositive donors with CMV antigen can generate CMV-specific, Leu-3-positive CTL that are primarily restricted in their activity to autologous and Class II, HLA-DR matched targets. Addition of either interleukin-1 (IL-1) or interleukin-2 (IL-2) to CMV antigen treated lymphocytes enhanced anti-CMV CTL activity in five of six donors tested. Neither natural killer cell nor lymphoproliferative activity was significantly affected by this treatment. Anti-CMV CTL response using lymphocytes from three HTLV-III seropositive and one HTLV-III seronegative homosexual donors was not augmented by the in vitro use of IL-1 or IL-2. This was in contrast to the enhanced response of the heterosexual control lymphocytes assayed simultaneously with these donors. This may represent an early defect in these individuals which may predispose them to other opportunistic infections and possibly the development of AIDS. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No: AAD87-02026)
Keywords: Cytomegalovirus/*IMMUNOLOGY Cytomegalovirus Infections/*IMMUNOLOGY Cytotoxicity, Immunologic Human HLA-DR Antigens/*GENETICS T-Lymphocytes/*IMMUNOLOGY THESIS
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
