Unresponsiveness to Mlsa induced in newborn Mlsb mice by maternal preimmunization.
Female BALB/c (H-2d, Mlsb) mice alloimmunized prior to and during syngeneic pregnancy with DBA/2 (H-2d, Mlsa) splenocytes gave rise to offspring with severely reduced responsiveness in adult life to DBA/2 stimulation in vitro mixed lymphocyte cultures. The offspring of the hyperimmunized mothers were also tolerant to neonatal challenge with large numbers of DBA/2 splenocytes, which resulted in runting disease of control neonatal BALB/c mice. Both challenged and unchallenged offspring of the immunized BALB/c mothers were hyporesponsive to DBA/2 but both stimulated and responded to normal BALB/c lymphocytes, indicating alteration in their T-cell repertoire. There was no reduction in the V beta 6-positive thymocyte subpopulation in the challenged or unchallenged offspring of the alloimmunized BALB/c mothers compared to normal controls, suggesting that hyporesponsiveness to DBA/2 is not due to thymic deletion of Mlsa-responsive clones. Examination of the T-cell subset composition of the hydrocortisone-resistant thymocytes and peripheral lymphocytes of the challenged and unchallenged groups of experimental mice revealed large increases in the percentage of Lyt-2+ T cells, sometimes accompanied by a decrease in the L3T4+ T-cell subset compared to age-matched control BALB/c. Lymphocytes from the hyporesponsive mice specifically suppressed the proliferative responses of control BALB/c to DBA/2 but not to AKR. The data indicate that maternal hyperimmunization can induce tolerance by a mechanism involving intrathymic selection of suppressor cells which can be combined with a negative selection of helper cells.
Matossian-Rogers
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Department of Immunology, Royal London Hospital Medical College, U.K.
DeGiorgi
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DeGiori
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D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D007108:Immune Tolerance; D007114:Immunization; D007959:Lymphocyte Culture Test, Mixed; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000954:Antigens, Surface; D016747:Minor Lymphocyte Stimulatory Antigens