Search for Suppression of T Cells Specific for the Second Nonhost H-2 Haplotype in F₁ → P Irradiation Bone Marrow Chimeras

Abstract

Irradiation bone marrow chimeras were made by lethally irradiating parental (P) mice and reconstituting them with T cell-depleted bone marrow cells from F₁ hybrid offsprings. These F₁ → 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 second parent's restriction specificity in the following tests of cytotoxic T cell activity against virus-infected targets: 1) 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 second parental type target cells. 2) Chimeric F₁ → P₁ lymphocytes did not suppress alloreactivity directed against the second parental H-2 type. 3) 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. 4) F₁ → P chimeric lymphocytes transferred to 500 R irradiated normal F₁ mice did not suppress reactivity for the second parental type targets. 5) F₁ → P chimeric lymphocytes or bone marrow cells transferred to lethally irradiated F₁ could still differentiate to express the second parental restriction specificity; similarly, when F₁ → P lymphocytes were mixed with normal but anti-ϑ plus complement-treated F₁ bone marrow cells and transferred to lethally irradiated F₁, both restriction specificities were generated.

Therefore, F₁ → P irradiation bone marrow chimeras as described and tested here do not contain mechanisms that suppress the restriction specificity of the second parent, which is not a host to the maturing F₁ T cells, at least at the effector stage or during differentiation.