Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: implications for vaccination of immunocompromised individuals.
Studies based on either MHC class II-knockout or CD4+ T cell-depleted murine models have demonstrated a critical role for CD4+ T cells in the generation of CD8+ T cell memory. However, it is difficult to extend these findings to immunocompromised humans where a complete loss of CD4+ T cells is rarely observed. Here, we have developed a model setting, which allows studies on the generation of CD8+ T cell memory responses in a transient CD4+ T cell-deficient setting similar to that seen in immunocompromised patients. Immunisation with an adenoviral vaccine under transient helpless or help-deficient conditions showed varying degrees of impact on the priming of CD8+ T cell responses. Antigen-specific T cells generated under normal CD4+ T cell help and transient help-deficient conditions showed similar effector phenotype and were capable of proliferation upon secondary antigen encounter. Most importantly, in spite of CD4+ T cell deficiency, the long-term CD8+ T cell memory response remained functionally stable and showed comparable cytotoxic effector function as seen in CD8+ T cells generated with normal CD4+ T cell numbers. These findings provide evidence that in spite of partially impaired activation of a primary CD8+ T cell response, a fully functional and stable memory CTL response can be induced under conditions of severe transient CD4+ T cell deficiency.
Smith
Corey
C
Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Australia.
Martinez
Michelle
M
Cooper
Leanne
L
Rist
Michael
M
Zhong
Jie
J
Khanna
Rajiv
R
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D016867:Immunocompromised Host; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008822:Mice, Transgenic; D014614:Vaccines, Synthetic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma; C417029:EBV-encoded nuclear antigen 1