Maternal tolerance is not critically dependent on interleukin-4.
Pregnant animals can generate and maintain immune responses to fetal antigens. This however, does not usually lead to fetal loss. At least two types of immune response are recognized. T helper type 1 (Th1) responses support the generation of cellular cytotoxicity. In contrast, Th2-type responses support the production of non-cytotoxic antibody and suppress the Th1-type. One attempt to explain why the fetus is not generally rejected has been to suggest that during pregnancy Th2-type responses are dominant. These responses rely heavily on interleukin-4 (IL-4) for both functions. This work focuses on maternal immunity to the male antigen H-Y, which is expressed in male fetuses. When injected with male spleen cells, female mice of certain strains mount a cytotoxic immune response to H-Y. However, pregnant females immunized in this way do not deliver litters with fewer males. To help delineate the possible role of IL-4 in such maternal tolerance, female mice genetically deficient in IL-4 were studied. The results show that: (1) deficiency in maternal IL-4 does not affect fertility, (2) deficiency in IL-4 is not associated with selective loss of male offspring in unimmunized mice, (3) pregnancy does not obliterate anti-H-Y reactivity in immunized mice and (4) maternal immunity to H-Y in the absence of IL-4 does not result in loss of male offspring. The results suggest that IL-4-dependent Th2-type responses are not critical to maternal tolerance. Other cytokines must be examined for their role in this phenomenon.
Bonney
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Laboratory of Gynecology, Immunology and Infectious Disease, Emory University School of Medicine, Department of Gynecology and Obstetrics, Atlanta, GA 30303, USA. ebonney@emory.edu
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D005298:Fertility / Q000276:immunology; D005313:Fetal Death / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006182:H-Y Antigen / Q000276:immunology; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000172:deficiency / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D012737:Sex Factors; D016038:Skin Transplantation / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D006182:H-Y Antigen; D015847:Interleukin-4