Differential requirement for CD4 help in the development of an antigen-specific CD8+ T cell response depending on the route of immunization.

Abstract

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.

• Authors: H Bour, C Horvath, C Lurquin, J C Cerottini, H R MacDonald
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 160 Issue 11 Pg. 5522-9 (Jun 01 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9605156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-C Antigens
• HLA-C*03 antigen
• Receptors, Antigen, T-Cell, alpha-beta
• L-Selectin

Topics

• Adoptive Transfer (methods)
• Animals
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cytotoxicity, Immunologic
• Epitopes, T-Lymphocyte (immunology)
• Female
• Genes, MHC Class I
• HLA-C Antigens (administration & dosage, immunology)
• Immunologic Memory
• Injections, Intradermal
• Injections, Intraperitoneal
• Kinetics
• L-Selectin (analysis)
• Lymphocyte Activation
• Mast-Cell Sarcoma
• Mice
• Mice, Inbred DBA
• Mice, Nude
• Neoplasm Transplantation
• Receptors, Antigen, T-Cell, alpha-beta (analysis)
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• T-Lymphocytes, Helper-Inducer (immunology)
• Transfection (immunology)
• Tumor Cells, Cultured