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From the Department of Microbiology, The University of Michigan Medical School, Ann Arbor, Michigan 48104
Abstract
Terminal dilution, adoptive cell transfer techniques were developed to quantify the protective effect of lymphoid cells in the pathogenesis of immune polioencephalomyelitis (IPE). The pathogenetic effects of lymphoid cell populations were quantified by deleting the step of antigenic challenge. Regression curves were computer analyzed and PD50 values were compared. Immune spleen cells (ISC) from 4- to 6-week-old donors were more protective (PD50 = 4.9 ± 1.3) than ISC from 12-month-old animals (PD50 > 7.0). The slopes of the regression curves also differed markedly (young mice, - 0.24; old mice, - 0.09). ISC were less protective in 12-month-indicator mice than in 5-month-old recipients (PD50 values of 5.2 ± 0.8 and 3.7 ± 0.8, respectively). When adoptive cell transfer tests were used to quantify the pathogenetic effects of donor cells it was found that ISC were pathogenetic at doses of 105 or less, but protective at higher doses. IPEC were pathogenetic at all test doses. When ISC were x-irradiated or sonicated they were only pathogenetic. Normal spleen or peritoneal exudate cells were neither protective nor pathogenetic.
A model was developed in which mice were either thymectomized mectomized at birth (Tx), or Tx at birth and x-irradiated (500 R) 8 weeks later (Tx-XR). Sham Tx or Tx-XR mice served as controls. All of the mice were challenged with antigen (104 x-irradiated Ib cells). Only a portion (8/24) of the Tx mice developed IPE, indicating that resistance was T cell dependent but also involved a significant T cell independent component. The data also indicated that T cells were not pathogenetic effector cells in this model. Tx mice were not reconstituted by ISC (7/18 developed IPE), Tx-XR mice were partially reconstituted (3/12 developed IPE), but sham Tx-XR were fully restored (0/20 had IPE). Normal spleen cells did not reconstitute any of the mice.
Footnotes
1 This work was supported by Grant NS09933 from the National Institute of Neurological Disease and Stroke.
2 Present address: Department of Microbiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284.
3 Present address: Department of Microbiology and Immunology, University of Minnesota School of Medicine, Duluth, Minnesota 55812.
4 Present address: Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486.
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