Differential requirement for CD4 help in the development of an antigen-specific CD8+ T cell response depending on the route of immunization.
Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a dramatic expansion of activated CD8+CD62L- T cells expressing exclusively the Vbeta10 segment. We have used this model to study the regulatory mechanisms involved in the development of the CW3-specific CD8+ response, with respect to different routes of immunization. Whereas both intradermal (i.d.) and i.p. immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of CD8+CD62L-Vbeta10+ cells, only the i.d. route allowed this expansion after immunization with P815 cells transfected with a minigene coding for the antigenic epitope CW3 170-179 (P815 miniCW3). Furthermore, depletion of CD4+ T cells in vivo completely abolished the specific response of CD8+CD62L-Vbeta10+ cells and prevented the rejection of P815-CW3 tumor cells injected i.p., whereas it did not affect CD8S+CD62L-Vbeta10+ cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8+ memory response was identical whether or not CD4+ T cells were depleted during the primary response. Collectively, these results suggest that the CD8+ T cell response to P815-CW3 tumor cells injected i.p. is strictly dependent upon recognition of a helper epitope by CD4+ T cells, whereas no such requirement is observed for i.d. injection.
Bour
H
H
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
Horvath
C
C
Lurquin
C
C
Cerottini
J C
JC
MacDonald
H R
HR
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I; D015236:HLA-C Antigens / Q000008:administration & dosage* / Q000276:immunology; D007156:Immunologic Memory; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D007700:Kinetics; D019041:L-Selectin / Q000032:analysis; D008213:Lymphocyte Activation; D012515:Mast-Cell Sarcoma; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019041:L-Selectin