CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4⁺T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

Abstract

Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs) derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA) were cocultured with CD4+ T cells derived from OT-II mice's (C57BL6/J-Tg(TcraTcrb)1100Mjb/J) spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU), activation of these cells (flow cytometry), cytokine profile (ELISA), and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

Uterine B Cells Exhibit Regulatory Properties During the Peri-Implantation Stage of Murine Pregnancy

“…Moreover, previous studies demonstrated the upregulated expression of CD80 and CD86 on murine splenic antigen presenting cells such as dendritic cells and macrophages at the pre-implantation period (day 3.5 pc). This was shown to be crucial in modulating T regulatory cell (Treg) abundance, cytokine production, and ultimately pregnancy outcome (33,34). A follow up study examining splenic B cells showed similar results, with CD86 protein expression significantly increased in normal pregnant mice compared to abortion-prone models at pre-implantation (35).…”

“…Likewise, the retention of differentiation markers CD24 and CD21 as well as expression of activation marker CD38 suggested that uterine B cells are mature, but yet to have differentiated into antibody-producing plasma cells (41,42). Furthermore, ∼20 and 50% of IL-10 negative uterine B cells express the ligands CD80 and CD86, respectively ( Figure 5B) which suggests that a significant proportion of the uterine B cells have the capacity for co-stimulating T cell activation, potentially leading to negative regulation by way of Treg expansion and modification of cytokine production (33,34). Interestingly, the small proportion observed as IL-10 + B cells within the uterine B cell population exhibited higher expression of co-stimulatory molecules CD80 and CD86 as well as CD27, an activation marker of memory and plasmablast lineages in murine B cells.…”

Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection

“…The upregulation of CD86 but not CD80 on APCs is observed in other diseases as well such as systemic lupus erythematosus [ 44 ]. In contrast to CD80, CD86 expression on APCs drives the differentiation of T cell towards a Th2 profile [ 12 , 13 , 14 , 15 , 16 ]. Previous studies showed that in chronic HBV-infected livers, most T cells are Th0-like cells and contribute to the production of Th2-type cytokines by producing IL-4 and IL-5 in addition to a low level of IFN-γ production [ 2 , 17 ].…”

“…On the other hand, CD80 and CD86 might have different roles in regulating the T helper (Th) responses. While CD80 expression on APCs mainly drives T cell differentiation towards a Th1 profile, CD86 leads the differentiation towards a Th2 profile [ 12 , 13 , 14 , 15 , 16 ]. Interestingly, during HBV infection T cell response, especially in liver infiltrating lymphocytes, is associated with the production of IL-10 and Th2 cytokines rather than Th1 cytokines, and Th1 responses are weak in chronic HBV-infected patients when compared with resolver [ 2 , 17 , 18 ].…”

The Role of Monocytes/Macrophages in HBV and HCV Infection

“…CD80 mainly drives T-cell diferentiation towards a Th1 proile and CD86 leads the diferentiation towards a Th2 proile [38][39][40][41][42]. T-cell response in HBV infection mainly initiates Th2 immune response rather than Th1.…”