Abstract
Infants with congenital CMV infection have a specific defect in CMV-induced lymphocyte proliferation, providing a model for investigation of mechanisms of viral immune recognition and immune response. In the present study the possible role of a defect in lymphokine activation of CMV-specific T helper cells (Th) was examined. IL-1 activity was detected in supernatants of patient mononuclear cell (MNC) cultures stimulated with CMV. In contrast, no IL-2 activity could be detected in supernatants of CMV-stimulated MNC cultures, whereas PHA induced normal IL-2 production. Addition of low concentrations of either crude TCGF or recombinant IL-2 (rIL-2) resulted in 2-4 fold augmentation of CMV-specific lymphocyte proliferation; exogenous IL-2 had no effect on MNC responses to HSV. CMV-specific Th lines/clones were established from three congenital CMV patients by initial stimulation of MNCs with CMV antigen and 0.1 U/ml rIL-2, followed by repeated stimulation with CMV, HLA-matched allogeneic feeder cells and 10% TCGF. The resulting CMV Th lines/clones proliferated specifically in response to stimulation with CMV antigen and produced endogenous IL-2. Thus, the immune deficiency associated with congenital CMV may either be due to an intrinsic defect in CMV-Th activation or CMV-specific suppressor cell activity.
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Selected References
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- Beck S., Barrell B. G. Human cytomegalovirus encodes a glycoprotein homologous to MHC class-I antigens. Nature. 1988 Jan 21;331(6153):269–272. doi: 10.1038/331269a0. [DOI] [PubMed] [Google Scholar]
- Faber W. R., Leiker D. L., Nengerman I. M., Zeijlemaker W. P., Schellekens P. T. Lymphocyte transformation test in leprosy: decreased lymphocyte reactivity to Mycobacterium leprae in lepromatous leprosy, with no evidence for a generalized impairment. Infect Immun. 1978 Dec;22(3):649–656. doi: 10.1128/iai.22.3.649-656.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujinami R. S., Nelson J. A., Walker L., Oldstone M. B. Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression. J Virol. 1988 Jan;62(1):100–105. doi: 10.1128/jvi.62.1.100-105.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gehrz R. C., Fuad S., Liu Y. N., Bach F. H. HLA class II restriction of T helper cell response to cytomegalovirus (CMV). I. Immunogenetic control of restriction. J Immunol. 1987 May 15;138(10):3145–3151. [PubMed] [Google Scholar]
- Gehrz R. C., Linner K. M., Christianson W. R., Ohm A. E., Balfour H. H., Jr Cytomegalovirus infection in infancy: virological and immunological studies. Clin Exp Immunol. 1982 Jan;47(1):27–33. [PMC free article] [PubMed] [Google Scholar]
- Gehrz R. C., Liu Y. N., Peterson E. S., Fuad S. A. Role of antigen-presenting cells in congenital cytomegalovirus-specific immunodeficiency. J Infect Dis. 1987 Jul;156(1):198–202. doi: 10.1093/infdis/156.1.198. [DOI] [PubMed] [Google Scholar]
- Gehrz R. C., Marker S. C., Knorr S. O., Kalis J. M., Balfour H. H., Jr Specific cell-mediated immune defect in active cytomegalovirus infection of young children and their mothers. Lancet. 1977 Oct 22;2(8043):844–847. doi: 10.1016/s0140-6736(77)90782-6. [DOI] [PubMed] [Google Scholar]
- Hanshaw J. B. Congenital cytomegalovirus infection: a fifteen year perspective. J Infect Dis. 1971 May;123(5):555–561. doi: 10.1093/infdis/123.5.555. [DOI] [PubMed] [Google Scholar]
- Haregewoin A., Godal T., Mustafa A. S., Belehu A., Yemaneberhan T. T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy. Nature. 1983 May 26;303(5915):342–344. doi: 10.1038/303342a0. [DOI] [PubMed] [Google Scholar]
- Hayward A. R., Herberger M. J., Groothuis J., Levin M. R. Specific immunity after congenital or neonatal infection with cytomegalovirus or herpes simplex virus. J Immunol. 1984 Nov;133(5):2469–2473. [PubMed] [Google Scholar]
- Liu Y. N., Fuad S., Gehrz R. C. Epstein-Barr virus-transformed lymphoblastoid cell lines as antigen-presenting cells and "augmenting" cells for human CMV-specific Th clones. Cell Immunol. 1987 Aug;108(1):64–75. doi: 10.1016/0008-8749(87)90193-6. [DOI] [PubMed] [Google Scholar]
- Liu Y. N., Kari B., Gehrz R. C. Human immune responses to major human cytomegalovirus glycoprotein complexes. J Virol. 1988 Mar;62(3):1066–1070. doi: 10.1128/jvi.62.3.1066-1070.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mehra V., Convit J., Rubinstein A., Bloom B. R. Activated suppressor T cells in leprosy. J Immunol. 1982 Nov;129(5):1946–1951. [PubMed] [Google Scholar]
- Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
- Modlin R. L., Kato H., Mehra V., Nelson E. E., Fan X. D., Rea T. H., Pattengale P. K., Bloom B. R. Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions. 1986 Jul 31-Aug 6Nature. 322(6078):459–461. doi: 10.1038/322459a0. [DOI] [PubMed] [Google Scholar]
- Ottenhoff T. H., Elferink D. G., Klatser P. R., de Vries R. R. Cloned suppressor T cells from a lepromatous leprosy patient suppress Mycobacterium leprae reactive helper T cells. 1986 Jul 31-Aug 6Nature. 322(6078):462–464. doi: 10.1038/322462a0. [DOI] [PubMed] [Google Scholar]
- Reynolds D. W., Dean P. H., Pass R. F., Alford C. A. Specific cell-mediated immunity in children with congenital and neonatal cytomegalovirus infection and their mothers. J Infect Dis. 1979 Oct;140(4):493–499. doi: 10.1093/infdis/140.4.493. [DOI] [PubMed] [Google Scholar]
- Rodgers B. C., Scott D. M., Mundin J., Sissons J. G. Monocyte-derived inhibitor of interleukin 1 induced by human cytomegalovirus. J Virol. 1985 Sep;55(3):527–532. doi: 10.1128/jvi.55.3.527-532.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sredni B., Schwartz R. H. Antigen-specific, proliferating T lymphocyte clones. Methodology, specificity, MHC restriction and alloreactivity. Immunol Rev. 1981;54:187–223. doi: 10.1111/j.1600-065x.1981.tb00438.x. [DOI] [PubMed] [Google Scholar]
- Starr S. E., Tolpin M. D., Friedman H. M., Paucker K., Plotkin S. A. Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers. J Infect Dis. 1979 Oct;140(4):500–505. doi: 10.1093/infdis/140.4.500. [DOI] [PubMed] [Google Scholar]
