DEVELOPMENT AND ANTIGEN-SPECIFICITY OF CD8(-LYMPHOCYTES IN BETA(2)-MICROGLOBULIN-NEGATIVE, MHC CLASS I-DEFICIENT MICE IN RESPONSE TO IMMUNIZATION WITH TUMOR-CELLS() CYTOTOXIC T)
Sg. Apasov et Mv. Sitkovsky, DEVELOPMENT AND ANTIGEN-SPECIFICITY OF CD8(-LYMPHOCYTES IN BETA(2)-MICROGLOBULIN-NEGATIVE, MHC CLASS I-DEFICIENT MICE IN RESPONSE TO IMMUNIZATION WITH TUMOR-CELLS() CYTOTOXIC T), The Journal of immunology, 152(5), 1994, pp. 2087-2097
beta(2)-Microglobulin knockout mice (beta(2)-m-/-) with MHC class I ex
pression 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 h
ighly lytic CD8(+) CTLs in the peritoneum and causes the local recruit
ment of CD8(+) T cells into lymph nodes and spleens of immune animals.
The accumulation of CD8(+) CTLs in peritoneum is accompanied by the r
ejection of tumor cells and the survival of animals. The deficiency in
MHC class I expression in beta(2)-m-/- mice is reflected in the delay
ed tumor rejection and CD8(+) cell accumulation during the primary ant
i-tumor response in comparison with normal mice. The secondary respons
e, however, is identical in normal and MHC class I-deficient mice. The
rejection of tumor cells appears to be MHC class I directed because n
o rejection of tumors, no accumulation oi CD8(+) CTLs, and no survival
of animals were observed when syngeneic tumor cells were used for inj
ection with the notable exception of anti-minor Ag response. The Ag sp
ecificity of CD8(+) CTLs in beta(2)-m-/- mice is demonstrated using a
panel of tumor target cells and class I transfectants. Although no sub
stantial differences were found in the number and specificity of perit
oneal CD8(+) CTLs in beta(2)-m-/- and normal mice using tumor rejectio
n studies, the analysis of TCR-V beta phenotype using the panel of mAb
s revealed the reduction in proportion of TCR-V beta 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 o
bserved after footpad immunization of beta(2)-m-/- mice with TNP-label
ed C57BL/6 splenocytes, suggesting anti-minor Ag reaction.