Apasov SG and Sitkovsky MV:
Development and antigen specificity of CD8+ cytotoxic T lymphocytes
in beta 2-microglobulin-negative, MHC class I-deficient mice in
response to immunization with tumor cells.
Journal of Immunology 1994 Mar 1;152(5):2087-97
ABSTRACT
beta 2-Microglobulin knockout mice (beta 2-m-/-) with MHC class I
expression deficiency are able to develop functional TCR(+)-alpha
beta, CD8+ CTLs in response to tumor cell injection. The i.p.
injection of beta 2-m-/- mice with tumor results in the massive
accumulation of highly lytic CD8+ CTLs in the peritoneum and causes
the local recruitment of CD8+ T cells into lymph nodes and spleens
of immune animals. The accumulation of CD8+ CTLs in peritoneum is
accompanied by the rejection of tumor cells and the survival of
animals. The deficiency in MHC class I expression in beta 2-m/- mice
is reflected in the delayed tumor rejection and CD8+ cell
accumulation during the primary anti-tumor response in comparison
with normal mice. The secondary response, however, is identical in
normal and MHC class I-deficient mice. The rejection of tumor cells
appears to be MHC class I directed because no rejection of tumors,
no accumulation of CD8+ CTLs, and no survival of animals were
observed when syngeneic tumor cells were used for injection with the
notable exception of anti-minor Ag response. The Ag specificity of
CD8+ CTLs in beta 2-m-/- mice is demonstrated using a panel of tumor
target cells and class I transfectants. Although no substantial
differences were found in the number and specificity of peritoneal
CD8+ CTLs in beta 2-m-/- and normal mice using tumor rejection
studies, the analysis of TCR-V beta phenotype using the panel of
mAbs revealed the reduction in proportion of TCR-V beta 5 and TCR-V
beta 6 used by CD8+ cell population from beta 2-m-/- mice.
Development of lytic and H-2-directed CD8+ cells in regional lymph
nodes was also observed after footpad immunization of beta 2-m-/-
mice with TNP-labeled C57BL/6 splenocytes, suggesting anti-minor Ag
reaction.
