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Role of Maternal Ig in the Induction of C-Specific CD8⁺ T Cell Tolerance¹

Département d’Immunologie, Institut Pasteur (Unité de Recherche Associée 161, Centre National de la Recherche Scientifique, et Université Pierre et Marie Curie), Paris, France

Although the influence of maternal Ig on the B cell repertoire and subsequent Ab response has been extensively studied, much less attention has been devoted to their effects on T cell responses of the offspring. To address this question, we have studied the influence of maternal -positive Ig (Ig) on the C-specific CD8⁺ T cell response of knock-out (-/-) pups resulting from various crosses and foster nursings. These systems allowed control of physiologic transmission of Ig at defined periods of ontogeny. Our data show that conventional transfer of maternal Ig via the placenta plus colostrum/milk or adoptive transfer via only the colostrum/milk were the most efficient at tolerizing C-specific CD8⁺ responses. Surprisingly, tolerance was not detected in -/- pups born to +/- females obtained by cesarean delivery and suckled by -/- mothers (transplacental supply only). Tolerance, which was strong until 5 wk of age, was reversible and waned with the decrease of Ig serum concentration. Depletion of CD4⁺ T cells at the time of C peptide immunization abolished the tolerance of C-specific CD8⁺ T cells. These data suggest that an oral supply of Ig is very efficient at inducing and maintaining tolerance of C-specific CD8⁺ T cells, at least for several weeks after birth, and that suppression rather than deletion is responsible for this tolerance. In addition, they strengthen the view that tolerance of CD8⁺ T cells to a soluble Ag is never permanently acquired even if it is present in large quantities during ontogeny.

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