A spontaneously arising pancreatic tumor does not promote the differentiation of naive CD8+ T lymphocytes into effector CTL.
In this report, we address whether a growing tumor provides sufficient inflammatory signals to promote activation, clonal expansion, and acquisition of effector functions by naive tumor-specific CD8(+) T lymphocytes. CD8(+) T lymphocytes obtained from hemagglutinin (HA)-specific clone 4 TCR-transgenic mice were injected into recipient mice that spontaneously develop pancreatic tumors expressing HA as a tumor-associated Ag (RIP-Tag2-HA mice). When 3 x 10(6) clone 4 CD8(+) T cells were transferred into tumor-bearing mice, the cells became activated in the pancreatic lymph nodes where they proliferated and acquired effector functions such as cytolytic activity and IFN-gamma production. Surprisingly, reducing the number of adoptively transferred CD8(+) T cells led to a parallel reduction in the proportion of the activated cells that exhibited effector functions, suggesting that CTL differentiation was induced by the large numbers of activated CD8(+) T cells and not the tumor environment. Provision of tumor-specific CD4(+) helper cells provided the signals required to promote both the development of CTL effector functions and increased clonal expansion, resulting in tumor eradication. Considering that only small numbers of tumor-specific CD8(+) T cells would be present in a conventional T cell repertoire, these data suggest that tumor growth alone may not provide the inflammatory signals necessary to support the development of CD8(+) T cell effector functions.
Lyman
Michael A
MA
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aung
Sandra
S
Biggs
Judith A
JA
Sherman
Linda A
LA
D019264:Adoptive Transfer; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D007328:Insulin / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology*; D011401:Promoter Regions, Genetic; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*
D000952:Antigens, Polyomavirus Transforming; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007328:Insulin; D011948:Receptors, Antigen, T-Cell