T Helper 1 and 2 Immune Responses in Relationship to Pregnancy, Nonpregnancy, Recurrent Spontaneous Abortions and Infertility of Repeated Implantation Failures

Abstract

It is becoming clear that during each developmental stage of pregnancy, different immunological conditions exist and may even be necessary for success. The widely accepted T helper (Th) 1 and 2 concept has some limitations if applied to the various developmental stages of pregnancy. During the implantation period, a multidirectional cytokine network is necessary with the blastocyst producing cytokines and other factors and the endometrium synthesizing factors necessary for the embryonic development. Improper immune responses and an unbalanced cytokine network may be related to implantation failures, pregnancy losses and obstetrical complications. A propensity to Th1 immune responses has been reported in these conditions systemically or locally. The presence of elevated Th1:Th2 cell ratios, high concentration of Th1 cytokines secreted by peripheral blood mononuclear cells, elevated NK cell cytotoxicity and levels, and emergence of various autoantibodies are the supporting evidence. The underlying immunopathology for the preponderance of Th1 is unknown. Genetic, environmental, and hormonal etiologies need to be explored further in the future. The purpose of this review is to give an overview of what is known about the immune response in women with reproductive failures and provide an update of some of the most recent findings in this field.

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…Such Th2 predominant response is the result of high levels of progesterone and oestrogen produced throughout all pregnancy [88]. The cytokine balance is directed toward a Th2 predominant response mainly after the second trimester of gestation [67] with strong Th1 immune responses during pregnancy resulting in maternal anaemia, spontaneous abortions and pre-term delivery [89].…”

Th1 and Th2 immune responses related to pelvic endometriosis

“…In several clinical situations, depending on the characteristics of each disease, such as AIDS 9 , cardiac 10 and neurological disorders 11 and in human reproduction 12 , a certain type of Th1/ Th2 immune response pattern is predominant. Our previous results showed that endometriosis is a complex disease with co-existence of both responses since we observed an increase in Interferon-gamma and IL-10 in patients with endometriosis when compared to a control group of patients without the disease 13 .…”

Associations between tumor necrosis factor-α and lymphotoxin-α polymorphisms and idiopathic recurrent miscarriage

“…This was evidenced by the association of increased Th2 cytokines with successful pregnancy, while heightened Th1 activity was indicative of poor pregnancy outcome, both in experimental animals and in humans (Hill et al 1995). In view of this interplay between (pro-inflammatory) Th1 and (anti-inflammatory) Th2 cells and their respective cytokines in pregnancy, dysregulated immunity stemming from altered Th1-Th2 balance was proposed as a potential mechanism underlying idiopathic RM in the face of unknown causes (Makhseed et al 2001, Kwak-Kim et al 2005.…”

“…Due to their pro-inflammatory and pro-apoptotic capacity, TNF-a and LT-a were described to mediate several aspects of pregnancy complications, including pre-eclampsia (Anim-Nyame et al 2003), miscarriage (Babbage et al 2001), and RM (Rezaei & Dabbagh 2002). Several mechanisms were proposed for the pro-abortogenic effects of TNF-a and LT-a, including trophoblast invasion and placentation (Kwak-Kim et al 2005) and induction of the expression of pro-apoptotic genes in human fetal membranes (Garcia-Lloret et al 2000), which in turn accelerates membrane degradation and thus increases the susceptibility to premature rupture (Fortunato et al 2001). TNF-a was also described to facilitate miscarriage indirectly by activating NK cells or macrophages (Raghupathy et al 2000).…”