A caveat for T cell transfer studies: generation of cytotoxic anti-Thy1.2 antibodies in Thy1.1 congenic mice given Thy1.2+ tumors or T cells

Abstract

Thy1.1 congenic B6.PL mice were used to simultaneously monitor Thy1.2+ E.G7-OVA tumors transplanted in the a.c. of the eye and i.v.-transferred tumor-specific Thy1.2+ CTLs to determine mechanisms that inhibit the tumoricidal activity of CTL responses in mice with established ocular tumors. Transferred CTLs were systemically deleted in mice with established ocular tumors. However, this deletion was not a unique mechanism of immune evasion by ocular tumors. Rather, development of Thy1.2+ tumors in the eye or skin of B6.PL mice generated cytotoxic anti-Thy1.2 antibodies that eliminated a subsequent Thy1.2+ T cell transfer. Anti-Thy1.2 immune responses in B6.PL mice were influenced by the route of antigen administration, as the serum concentration of cytotoxic anti-Thy1.2 antibodies was 92-fold greater in mice with eye tumors in comparison with mice with skin tumors. In addition, anti-Thy1.2 immune responses were detected in B6.PL mice given naïve Thy1.2+ T cells i.p. but not i.v. Anti-Thy1.2 responses were augmented in B6.PL mice with ocular Thy1.2+ EL-4 tumors that did not express OVA, suggesting immunodominance of OVA antigen over Thy1.2. Thy1.1+ T cells given i.p. was not immunogenic in Thy1.2 congenic mice. These data reaffirm that the introduction of antigens in the a.c. induces robust antibody responses. Experimentation using allotypic differences in Thy1 between donor cells and recipient mice must consider cytotoxic anti-Thy1 antibody generation in the interpretation of results.

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

“…In published work, donor T cells are generally well tolerated by recipient mice. Nevertheless, there are a few documented cases of immune responses elicited by transferred cells that differed at the CD45 or Thy1 loci [16][17][18][19][20]. While such donor/recipient pairs are often considered to be "congenic", it is clear that multiple genes are included in the congenic interval.…”

Bone marrow chimeras—a vital tool in basic and translational research

“…[ transplanted into donor mice expressing the other allotype (CD90.2) or wildtype background, respectively. These experiments showed that both factors are capable of triggering an immune response [35][36][37]. It should be kept in mind that mouse strains are differentially capable of mounting immune responses to certain tracking molecules, with BALB/c mice being more immunocompetent against eGFP than C57BL/6 [38].…”

Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity

“…The procedures used in this experiment have been published previously [ 33 ]. Briefly, splenocytes were harvested from CD45.2 + OT-1 mice, and CD8 + T cells were purified using the MACS CD8 + T Cell Isolation Kit (Miltenyi Biotec, Bergisch Gladbach, Germany), according to the manufacturer’s instructions.…”