Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

Am J Reprod Immunol. 2018 Sep;80(3):e12853. doi: 10.1111/aji.12853. Epub 2018 Mar 31.


Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi-allograft and so immunological dysregulation is considered as one of the important causes in repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It has been revealed that lymphocytes immunotherapy (LIT) could be an appropriate approach to prevent pregnancy loss in such patients. Various mechanisms have been suggested for effectiveness of LIT such as enhancing expression of anti-paternal cytotoxic antibodies (APCA), progesterone-induced blocking factor (PIBF), anti-idiotypic antibodies (Ab2), and mixed lymphocyte reaction blocking antibodies (MLR-Bf), as well as reduction in the T helper 1/T helper 2 ratio and deviation in the pattern of cytokines production. However, there are controversial results about the beneficial effect of LIT treatment in RIF and RPL patients. In the current study, we reviewed findings of LIT in RIF and RPL patients with a focus on possible mechanisms of alloimmunization in preserving pregnancy. Besides, we highlighted possible reasons for mixed results about the effectiveness of LIT and way of solving the problem. Also, we proposed potential laboratory and clinical criteria to recruit patients for LIT.

Keywords: implantation; lymphocytes immunotherapy; pregnancy; recurrent pregnancy loss; repeated implantation failure; reproductive immunology.

Publication types

  • Review

MeSH terms

  • Abortion, Habitual / immunology
  • Abortion, Habitual / therapy*
  • Animals
  • Antibodies, Blocking / therapeutic use
  • Female
  • Humans
  • Immunization
  • Immunotherapy, Adoptive / methods*
  • Isoantigens / immunology
  • Lymphocytes / immunology*
  • Pregnancy
  • Th1-Th2 Balance
  • Th2 Cells / immunology*


  • Antibodies, Blocking
  • Isoantigens