A new methodological principle permitting clonal analyses of lymphoid cells is being applied to investigate the dynamics of B cell activation and to improve the diagnosis of the human immunodeficiency viruses (HIV). Based on the enzyme-linked immunospot (ELISPOT) assays, co-discovered by a member of our group, these methods allow quantitative assessments, in the blood and other body fluids or tissues, of B cells secreting immunoglobulins (IG's) of different isotypes to specific antigens. Single cells releasing immunoreactive substances, such as viral antigens, can also be enumerated. These methods should circumvent several difficulties associated with HIV diagnosis, e.g. transplacentally- acquired antibodies in infants, or problems in defining immune responses with other assays, e.g. the possible effects of immune complexes or of competition between Ig isotypes for HIV antigens. We propose to apply the ELISPOT methodology in longitudinal studies of the offspring of HIV antibody positive pregnant women (routine prenatal testing in our hospital with 10,000 pregnant women a year indicates that already over 0.5% are HIV antibody positive). Together with the use of other virological (including polymerase chain reaction assays) and more conventional immunological tests, the information obtained would be particularly valuable in defining truly infected infants for therapeutic trials, in furthering our understanding of the immunobiology of the HIV- infected and non-infected infants, and in delineating the immunobiology of the HIV-infected adults and infants, providing support for the possibility of detecting and enumerating HIV antibody-secreting lymphocytes to specific viral proteins. Similarly, we have developed the methodology for the enumeration of immunoglobulin secreting cells of different isotypes in children and adults which should permit the B cell clonal proliferation so prominent in HIV-infected individuals, particularly children, to be monitored. Studies will also be performed to enumerate mononuclear cells (and subsets) releasing HIV antigens. The methodologies developed should provide important diagnostic and prognostic markers for current and eventual prevention (e.g. vaccine) or therapeutic (e.g. antiviral and immune modulator) interventions for HIV infection in individuals of all ages.

Project Start
1989-08-01
Project End
1992-11-30
Budget Start
1989-08-01
Budget End
1990-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Eriksson, K; Kilander, A; Hagberg, L et al. (1995) Intestinal immune responsiveness in HIV-infected individuals. Adv Exp Med Biol 371B:1011-4
Czerkinsky, C; Quiding, M; Eriksson, K et al. (1995) Induction of specific immunity at mucosal surfaces: prospects for vaccine development. Adv Exp Med Biol 371B:1409-16
Eriksson, K; Kilander, A; Hagberg, L et al. (1995) Virus-specific antibody production and polyclonal B-cell activation in the intestinal mucosa of HIV-infected individuals. AIDS 9:695-700
Czerkinsky, C; Holmgren, J (1994) Exploration of mucosal immunity in humans: relevance to vaccine development. Cell Mol Biol (Noisy-le-grand) 40 Suppl 1:37-44
Ibegbu, C; Spira, T J; Nesheim, S et al. (1994) Subpopulations of T and B cells in perinatally HIV-infected and noninfected age-matched children compared with those in adults. Clin Immunol Immunopathol 71:27-32
Nahmias, A; Ibegbu, C; Lee, F et al. (1994) The development of the immune system--importance in the ascertainment of immunophenotypic changes in perinatal HIV infection. Clin Immunol Immunopathol 71:2-7
Eriksson, K; Kilander, A; Hagberg, L et al. (1993) Intestinal antibody responses to oral vaccination in HIV-infected individuals. AIDS 7:1087-91
Stoll, B J; Lee, F K; Larsen, S et al. (1993) Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. J Infect Dis 167:1093-9
Stoll, B J; Lee, F K; Hale, E et al. (1993) Immunoglobulin secretion by the normal and the infected newborn infant. J Pediatr 122:780-6
Eriksson, K; Nordstrom, I; Horal, P et al. (1992) Amplified ELISPOT assay for the detection of HIV-specific antibody-secreting cells in subhuman primates. J Immunol Methods 153:107-13

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