Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4−/− hosts, whereas memory CD8 cells generated in CD4−/− mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.

[1]  E. Wherry,et al.  Vaccines: Effector and memory T-cell differentiation: implications for vaccine development , 2002, Nature Reviews Immunology.

[2]  J. Whitton,et al.  A "string-of-beads" vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge , 1993, Journal of virology.

[3]  J. Altman,et al.  Postexposure vaccination massively increases the prevalence of gamma-herpesvirus-specific CD8+ T cells but confers minimal survival advantage on CD4-deficient mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Doherty,et al.  Diminished Primary and Secondary Influenza Virus-Specific CD8+ T-Cell Responses in CD4-Depleted Ig−/− Mice , 2000, Journal of Virology.

[5]  Stephen P. Schoenberger,et al.  T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions , 1998, Nature.

[6]  Hao Shen,et al.  Cutting Edge: CD4 and CD8 T Cells Are Intrinsically Different in Their Proliferative Responses1 , 2002, The Journal of Immunology.

[7]  J. Altman,et al.  Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function , 1998, The Journal of experimental medicine.

[8]  R. Ahmed,et al.  Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection 1 , 2003, The Journal of Immunology.

[9]  C. Janeway,et al.  Innate immune recognition. , 2002, Annual review of immunology.

[10]  P. Doherty,et al.  Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of γ-Herpesvirus-Infected CD4-Deficient Mice1 , 2002, The Journal of Immunology.

[11]  M. Bevan,et al.  A novel helper role for CD4 T cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. V. von Herrath,et al.  CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge , 1996, Journal of virology.

[13]  Urs Christen,et al.  CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes , 2003, Nature.

[14]  J. Altman,et al.  Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. , 1998, Immunity.

[15]  Richard A. Flavell,et al.  Help for cytotoxic-T-cell responses is mediated by CD40 signalling , 1998, Nature.

[16]  Polly Matzinger,et al.  A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell , 1998, Nature.

[17]  B. Rocha,et al.  A Role for CD40 Expression on CD8+ T Cells in the Generation of CD8+ T Cell Memory , 2002, Science.

[18]  M. Plebanski,et al.  Induction of CD8+ T cells using heterologous prime‐boost immunisation strategies , 1999, Immunological reviews.

[19]  R. Ahmed,et al.  CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection , 1994, Journal of virology.

[20]  M. Schilham,et al.  Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4 , 1991, Nature.