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.
McKenna KC1, Vicetti Miguel RD, Beatty KM, Bilonick RA.
1University of Pittsburgh, Eye and Ear Institute, Pittsburgh, PA 15213, USA. mckennakc@upmc.edu
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.
J Leukoc Biol. 2011 Feb;89(2):291-300. doi: 10.1189/jlb.0610333. Epub 2010 Oct 19.
http://www.jleukbio.org/content/89/2/291.long
Md. Rodolfo Vicetti. Ex-miembro del GII.
