Search for suppression of T cells specific for the second nonhost H-2 haplotype in F1 leads to P irradiation bone marrow chimeras
Zinkernagel, R.M.; Althage, A.
Journal of Immunology 122(5): 1742-1749
1979
ISSN/ISBN: 0022-1767 PMID: 156219 Document Number: 151383
Irradiation bone marrow chimeras were made by lethally irradiating parental (P) mice and reconstituting them with T [thymus-derived] cell-depleted bone marrow cells from F1 hybrid offsprings. These F1 .fwdarw. P chimeric lymphocytes were then analyzed for suppressor mechanisms that could cause the differentiation of effector T cells whose responsiveness was restricted in specificity to the host parent's H-2 haplotype. No evidence was detected for acute or chronic suppression of the 2nd parent's restriction specificity in the following tests of cytotoxic T cell activity against virus-infected targets. Mixing normal F1 spleen cells with various amounts of chimeric spleen and lymph node cells during the cytotoxicity test or, during sensitization in F1 mice tested 5 days after irradiation and infection, revealed no suppression of the activity for the 2nd parental type target cells. Chimeric F1 .fwdarw. P1 lymphocytes did not suppress alloreactivity directed against the 2nd parental H-2 type. Presence or absence of T cells in the transferred, reconstituting F1 bone marrow cells did not change the hosts' influence on the selection of restriction specificity. F1 .fwdarw. P chimeric lymphocytes transferred to 500 R irradiated normal F1 mice did not suppress reactivity for the 2nd parental type targets. F1 .fwdarw. P chimeric lymphocytes or bone marrow cells transferred to lethally irradiated F1 could still differentiate to express the 2nd parental restriction specificity. Similarly, when F1 .fwdarw. P lymphocytes were mixed with normal but anti-.theta. plus complement-treated F1 bone marrow cells and transferred to lethally irradiated F1, both restriction specificities were generated. F1 .fwdarw. P irradiation bone marrow chimeras as described and tested do not contain mechanisms that suppress the restriction specificity of the 2nd parent, which is not a host to the maturing F1 T cells, at least at the effector stage or during differentiation.