Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: implications for vaccination of immunocompromised individuals. Export

@article{citeulike:3449357, abstract = {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.}, author = {Smith, C. and Martinez, M. and Cooper, L. and Rist, M. and Zhong, J. and Khanna, R.}, citeulike-article-id = {3449357}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/eji.200737933}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18506880}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18506880}, doi = {10.1002/eji.200737933}, issn = {0014-2980}, journal = {European journal of immunology}, keywords = {cd4, cd8, deficiency, immunocompromised, memory, vaccination}, month = {July}, number = {7}, pages = {1857--1866}, posted-at = {2008-10-25 04:28:19}, priority = {2}, title = {Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: implications for vaccination of immunocompromised individuals.}, url = {http://dx.doi.org/10.1002/eji.200737933}, volume = {38}, year = {2008} }

TY - JOUR ID - citeulike:3449357 L3 - citeulike-article-id:3449357 N2 - 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. IS - 7 JF - European journal of immunology SN - 0014-2980 EP - 1866 TI - Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: implications for vaccination of immunocompromised individuals. VL - 38 SP - 1857 KW - cd4 KW - cd8 KW - deficiency KW - immunocompromised KW - memory KW - vaccination AU - Smith, C AU - Martinez, M AU - Cooper, L AU - Rist, M AU - Zhong, J AU - Khanna, R PY - 2008/07// UR - http://dx.doi.org/10.1002/eji.200737933 ER -