Precursor CTL specific for retrovirus-induced T lymphoma are found at high frequency in unprimed syngeneic mice.
The retrovirus-induced RBL5 lymphoma can be rejected by adoptive transfer of noncytolytic CD4+ Th 1 lymphocytes in normal hosts, without a requirement for transfer of specific CD8+ CTL. Therefore, we hypothesized that host precursor CTL (pCTL) might cooperate with transferred CD4+ Th1 cells to mediate tumor rejection. To evaluate this hypothesis, lymphocytes from non-immunized mice were analyzed for cytolytic activity after short-term bulk lymphocyte tumor culture (BLTC) with rIL-2 (5U/ml). BLTC induced the differentiation of anti-RBL5 CTL distinct from non-MHC-restricted LAK. These effectors were CD8+, TCR alpha/beta+, and utilized the CD3-TCR complex for MHC class I-restricted lysis. The majority of pCTL were found within the CD44/PgP-1hi population of memory/activated lymphocytes. However, there was no serologic evidence for prior exposure to RBL5-related tumor or viral Ags. CTL activity was susceptible to partial blockade with mAbs directed against CD8 and MHC class I, suggesting a relatively low-affinity Ag-TCR interaction. These data are most consistent with the recruitment of a population of Ag-specific, but cross-reactive, pCTL during BLTC.
Moutschen
M P
MP
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Shan
H
H
Giantonio
B J
BJ
Bookman
M A
MA
D000818:Animals; D000957:Antigens, Viral, Tumor; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006084:Graft Rejection; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology; D011925:Rauscher Virus; D012192:Retroviridae Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014185:Transplantation, Isogeneic; D014412:Tumor Virus Infections / Q000276:immunology*
D000957:Antigens, Viral, Tumor; D007376:Interleukin-2