Lack of T cell tolerance in mice exposed to a protein antigen through lactation.
Offspring of mother mice treated immediately after delivery with deaggregated human gamma-globulins (dHGG) are unable to produce HGG-specific antibodies when challenged with immunogenic forms of HGG (HGG/CFA) in adulthood. Despite a defective antibody response, animals rendered tolerant to HGG as neonates retain tolerogen-specific T cells able to proliferate and secrete lymphokines. The pattern of IL-2 and IL-4 secretion by T cells isolated from tolerant animals could not be distinguished from the corresponding cells in control mice, suggesting that neonatal exposure to dHGG did not affect T cell reactivity or Th1/Th2 in vivo balance. Moreover, immunization of tolerant animals with haptenated HGG confirmed the presence of tolerogen-specific helper T cells in vivo. Functional T cell depletion by anti-CD3 mAbs during lactation failed to modify induction of B cell tolerance, suggesting that T cells are neither affected nor required to induce the selective tolerance status observed in this model. Based on the finding that antigen-presenting cell functions in secondary organs (spleen, peritoneal cavity) are a late acquisition during ontogeny and reach adult-like levels at weaning, we propose that most soluble proteins elude T cell recognition during lactation due to defective antigen presentation.
Ryelandt
M
M
Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Rhode-Saint-Genèse, Belgium.
De Wit
D
D
Van Mechelen
M
M
Vansanten
G
G
Urbain
J
J
Leo
O
O
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007774:Lactation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D005719:gamma-Globulins / Q000276:immunology; D010132:p-Azobenzenearsonate / Q000276:immunology
D000941:Antigens; D007376:Interleukin-2; D005719:gamma-Globulins; D015847:Interleukin-4; D010132:p-Azobenzenearsonate