Direct Recognition of Rat MHC Antigens on Rat Antigen-Presenting Cells by Mouse Cd4+ and Cd8+ T Cells and Establishment of T Cell Clones Exhibiting a Direct Recognition Pathway1

Abstract

Alloantigens are recognized by T cells either through a direct pathway, which involves recognition of alloantigens expressed on allogeneic antigen-presenting cells (APC), or through an indirect pathway, which involves recognition of processed alloantigens presented by self APC. We investigated whether rat xenoantigens are also recognized by direct (xenogeneic APC-restricted) and/or indirect (self APC-restricted) pathways. C57BL/6 (B6) mouse anti-F344 or WKAH rat mixed lymphocyte reactions (MLRs) were partially inhibited by addition of either anti-mouse CD4 or CD8 monoclonal antibody (mAb) and almost completely blocked in the presence of both mAbs. These xenogeneic MLRs were almost completely inhibited by simultaneous depletion of both self and xeno APCs and only partially suppressed by the elimination of either type of APC, indicating that freshly prepared splenic mouse T cells can recognize rat xenoantigens through both direct and indirect pathways. Anti-F334 T cell lines were generated from B6 anti-F344 MLR cultures, and four CD4+ and four CD8+ T cell clones were isolated from these parental lines. The parental lines and those derived T cell clones were tested for their ability to proliferate depending on the presence of F344 APC. Proliferation of CD8 clones by stimulation with F344 APC was inhibited by the addition of anti-rat class I MHC mAb but not of anti-class II MHC mAbs. Conversely, proliferation of CD4 clones was reduced by addition of anti-class II MHC mAbs. Thus, these results indicate that xeno (rat)-reactive mouse T cells recognize xenoantigens via both indirect (self APC-restricted) and direct (xeno APC-restricted) pathways and that both CD4 and CD8 subsets of T cells participate in a direct pathway of xenoantigen recognition.

Double-Negative T Cells, Activated by Xenoantigen, Lyse Autologous B and T Cells Using a Perforin/Granzyme-Dependent, Fas-Fas Ligand-Independent Pathway

“…First, stimulation of DNT cells requires murine TCR-rat MHC I or II molecule interaction (Fig. 1a) (48). Second, we would expect that other stimulatory signals should be involved in DNT cell activation by xenoantigen, given the absence of classical stimulatory factors such as CD4, CD8, CD28, CD40L, 4-1BB, ICOS, and OX40 on DNT cells in our staining study.…”

Rat‐to‐mouse small bowel xenotransplantation: A novel model for studying acute vascular and hyperacute xenograft rejection and xenogenic cell migration

“…Guinea pig‐to‐rat small bowel xenografting results in the typical changes of hyperacute rejection (HAR) [2]. In this paper, we established new models of small bowel xenografting in rat‐to‐mouse combination, which have the potential advantages include: (1) rat‐to‐mouse transplantation induces both direct and indirect T cell recognition to xeno‐antigens, similar in pig‐to‐human xenografting [8–10]; (2) the availability of knock‐out animal to dissect immune responses; and (3) access to a wide range of monoclonal antibodies (mAbs) to study antigen expression, cell trafficking, etc. As reported herein, these small bowel grafts develop aggressive acute vascular rejection and vigorous recipient‐to‐graft cell migration by 5 days.…”

Functional roles of microglia in neural tissue transplantation / by Nathan Adam Pennell.

“…It has been speculated that the presence of antigen presenting cells (APCs) within the donor tissue is the primary stimulus for the onset of graft rejection, as these cells may present foreign antigen directly to host T-cells (Lawrence et al, 1990;Nicholas and Arnason, 1989;VanBuskirk et al. 1994;Hirota et al, 1997).…”