Abstract

The objectives of this grant are to characterize the cellular immune responses to Epstein-Barr virus (EBV) and to define the immunoregulatory events important in successful control of EBV infection during acute infectious mononucleosis (IM). We will continue our studies to further characterize the in vivo EBV induced MHC-nonrestricted cytotoxic T-cells (anomalous T-killer cells). The T cell lineage of these anomalous T-killer cells will be established by looking for molecular rearrangement of the T cell receptor genes. We will determine whether these T-killer cells are directed against EBV antigens and test the hypothesis that they are in fact alloreactive T-cells directed at altered class I molecules. Anomalous T-killer cells will be cloned to further prove polyclonality and determine target cell specificities. We plan to investigate the immunoregulatory role of in vivo EBV induced activated helper/inducer T cells. We will use CD4 helper/inducer T cell monoclonals to identify functionally distinct subpopulations. These subpopulations will be functionally studied in assays to evaluate help and suppression of B cell and T cell function. Cloning studies will be attempted to look at function at the clonal level. The long-term objective of our laboratory is to better understand the immunoregulatory events which occur during acute EBV infection. This knowledge will be used to understand immune defects which predispose individuals to fatal infection and lymphoproliferative disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025542-04
Application #
3138979
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Swaminathan, S; Hesselton, R; Sullivan, J et al. (1993) Epstein-Barr virus recombinants with specifically mutated BCRF1 genes. J Virol 67:7406-13
Moore, J P; Sattentau, Q J; Yoshiyama, H et al. (1993) Probing the structure of the V2 domain of human immunodeficiency virus type 1 surface glycoprotein gp120 with a panel of eight monoclonal antibodies: human immune response to the V1 and V2 domains. J Virol 67:6136-51
Hesselton, R M; Koup, R A; Cromwell, M A et al. (1993) Human peripheral blood xenografts in the SCID mouse: characterization of immunologic reconstitution. J Infect Dis 168:630-40
Moore, J P; Thali, M; Jameson, B A et al. (1993) Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1: probing the structure of the C4 and V4 domains and the interaction of the C4 domain with the V3 loop. J Virol 67:4785-96
Moore, J P; Yoshiyama, H; Ho, D D et al. (1993) Antigenic variation in gp120s from molecular clones of HIV-1 LAI. AIDS Res Hum Retroviruses 9:1185-93
Conley, M E; Sullivan, J L; Neidich, J A et al. (1990) X chromosome inactivation patterns in obligate carriers of X-linked lymphoproliferative syndrome. Clin Immunol Immunopathol 55:486-91
Skare, J C; Sullivan, J L; Milunsky, A (1989) Mapping the mutation causing the X-linked lymphoproliferative syndrome in relation to restriction fragment length polymorphisms on Xq. Hum Genet 82:349-53
Tomkinson, B E; Brown, M C; Ip, S H et al. (1989) Soluble CD8 during T cell activation. J Immunol 142:2230-6
Ho, D D; Bredesen, D E; Vinters, H V et al. (1989) The acquired immunodeficiency syndrome (AIDS) dementia complex. Ann Intern Med 111:400-10
Skare, J C; Grierson, H L; Sullivan, J L et al. (1989) Linkage analysis of seven kindreds with the X-linked lymphoproliferative syndrome (XLP) confirms that the XLP locus is near DXS42 and DXS37. Hum Genet 82:354-8

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