• 1
    Blattman JN, Antia R, Sourdive DJ, Wang X, Kaech SM, Murali-Krishna K, Altman JD, Ahmed R. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J Exp Med 2002; 195:65764.
  • 2
    Obar JJ, Khanna KM, Lefrancois L. Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity 2008; 28:85969.
  • 3
    Rizzuto GA, Merghoub T, Hirschhorn-Cymerman D et al. Self-antigen-specific CD8+ T cell precursor frequency determines the quality of the antitumor immune response. J Exp Med 2009; 206:84966.
  • 4
    Umeshappa CS, Xiang J. Regulators of T-cell memory generation: TCR signals versus CD4+ help? Immunol Cell Biol 2011; 89:57880.
  • 5
    Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 1998; 393:47880.
  • 6
    Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ. T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions. Nature 1998; 393:4803.
  • 7
    Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 1998; 393:4748.
  • 8
    Umeshappa CS, Huang H, Xie Y, Wei Y, Mulligan SJ, Deng Y, Xiang J. CD4+ Th-APC with acquired peptide/MHC class I and II complexes stimulate type 1 helper CD4+ and central memory CD8+ T cell responses. J Immunol 2009; 182:193206.
  • 9
    Bourgeois C, Rocha B, Tanchot C. A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory. Science 2002; 297:20603.
  • 10
    Karanikas V, Zamanakou M, Soukou F, Kerenidi T, Gourgoulianis KI, Germenis AE. Naturally occurring tumor-specific CD8+ T-cell precursors in individuals with and without cancer. Immunol Cell Biol 2011; 88:57585.
  • 11
    Ford ML, Wagener ME, Hanna SS, Pearson TC, Kirk AD, Larsen CP. A critical precursor frequency of donor-reactive CD4+ T cell help is required for CD8+ T cell-mediated CD28/CD154-independent rejection. J Immunol 2008; 180:720311.
  • 12
    Ford ML, Koehn BH, Wagener ME, Jiang W, Gangappa S, Pearson TC, Larsen CP. Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation. J Exp Med 2007; 204:299309.
  • 13
    Marzo AL, Sowell RT, Scott B. The role of precursor frequency in the differentiation of memory T cells: memory by numbers. Adv Exp Med Biol 2010; 684:6978.
  • 14
    Marzo AL, Klonowski KD, Le Bon A, Borrow P, Tough DF, Lefrancois L. Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nat Immunol 2005; 6:7939.
  • 15
    Jooss J, Eiermann TH, Wagner H, Kabelitz D. Interleukin 2 production by alloantigen-stimulated CD4+ and CD8+ human T cell subsets: frequency of HLA class I or class II-reactive precursor cells and clonal specificity of activated T cells. Immunobiology 1989; 179:36681.
  • 16
    van den Berg H, Greuter M, Kraal G, den Haan JM. Different mechanisms regulate CD4+ T cell independent induction of oral and nasal tolerance of CD8+ T cells. Immunobiology 2010; 215:16371.
  • 17
    Somma P, Ristori G, Battistini L et al. Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis. J Leukoc Biol 2007; 81:696710.
  • 18
    Floyd TL, Orr SB, Coley SM, Hanna SS, Wagener ME, Kirk AD, Larsen CP, Ford ML. High-frequency alloreactive T cells augment effector function of low-frequency CD8+ T-cell responses under CD28/CD154 blockade. Transplantation 2010; 89:120817.
  • 19
    Ye Z, Ahmed KA, Huang J, Xie Y, Munegowda MA, Xiang J. T cell precursor frequency differentially affects CTL responses under different immune conditions. Biochem Biophys Res Commun 2008; 367:42734.
  • 20
    Xiang J, Huang H, Liu Y. A new dynamic model of CD8+ T effector cell responses via CD4+ T helper-antigen-presenting cells. J Immunol 2005; 174:7497505.
  • 21
    Wiesel M, Joller N, Ehlert AK, Crouse J, Sporri R, Bachmann MF, Oxenius A. Th cells act via two synergistic pathways to promote antiviral CD8+ T cell responses. J Immunol 2010; 185:518897.
  • 22
    Shi M, Hao S, Chan T, Xiang J. CD4+ T cells stimulate memory CD8+ T cell expansion via acquired pMHC I complexes and costimulatory molecules, and IL-2 secretion. J Leukoc Biol 2006; 80:135463.
  • 23
    Hernandez MG, Shen L, Rock KL. CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell help. J Immunol 2008; 180:438290.
  • 24
    Johnson S, Zhan Y, Sutherland RM et al. Selected Toll-like receptor ligands and viruses promote helper-independent cytotoxic T cell priming by upregulating CD40L on dendritic cells. Immunity 2009; 30:21827.
  • 25
    Murugaiyan G, Agrawal R, Mishra GC, Mitra D, Saha B. Differential CD40/CD40L expression results in counteracting antitumor immune responses. J Immunol 2007; 178:204755.
  • 26
    Hernandez MG, Shen L, Rock KL. CD40–CD40 ligand interaction between dendritic cells and CD8+ T cells is needed to stimulate maximal T cell responses in the absence of CD4+ T cell help. J Immunol 2007; 178:284452.
  • 27
    Mintern JD, Davey GM, Belz GT, Carbone FR, Heath WR. Cutting edge: precursor frequency affects the helper dependence of cytotoxic T cells. J Immunol 2002; 168:97780.
  • 28
    Novy P, Quigley M, Huang X, Yang Y. CD4 T cells are required for CD8 T cell survival during both primary and memory recall responses. J Immunol 2007; 179:824351.
  • 29
    Sun JC, Williams MA, Bevan MJ. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nat Immunol 2004; 5:92733.
  • 30
    Novy P, Huang X, Leonard WJ, Yang Y. Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection. J Immunol 2011; 186:272938.
  • 31
    Sherritt MA, Gardner J, Elliott SL, Schmidt C, Purdie D, Deliyannis G, Heath WR, Suhrbier A. Effect of pre-existing cytotoxic T lymphocytes on therapeutic vaccines. Eur J Immunol 2000; 30:6717.
  • 32
    Rahemtulla A, Fung-Leung WP, Schilham MW et al. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature 1991; 353:1804.
  • 33
    Shedlock DJ, Shen H. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 2003; 300:3379.
  • 34
    Jiao L, Han X, Wang S, Fan Y, Yang M, Qiu H, Yang X. Imprinted DC mediate the immune-educating effect of early-life microbial exposure. Eur J Immunol 2009; 39:46980.
  • 35
    Rapetti L, Meunier S, Pontoux C, Tanchot C. CD4 help regulates expression of crucial genes involved in CD8 T cell memory and sensitivity to regulatory elements. J Immunol 2008; 181:299308.
  • 36
    Klebanoff CA, Acquavella N, Yu Z, Restifo NP. Therapeutic cancer vaccines: are we there yet? Immunol Rev 2011; 239:2744.
  • 37
    Thomas-Kaskel AK, Waller CF, Schultze-Seemann W, Veelken H. Immunotherapy with dendritic cells for prostate cancer. Int J Cancer 2007; 121:46773.
  • 38
    Jahnisch H, Fussel S, Kiessling A et al. Dendritic cell-based immunotherapy for prostate cancer. Clin Dev Immunol 2010; 2010:517493.
  • 39
    Kiessling A, Fussel S, Wehner R, Bachmann M, Wirth MP, Rieber EP, Schmitz M. Advances in specific immunotherapy for prostate cancer. Eur Urol 2008; 53:694708.
  • 40
    Dokouhaki P, Han M, Joe B, Li M, Johnston MR, Tsao MS, Zhang L. Adoptive immunotherapy of cancer using ex vivo expanded human γδ T cells: a new approach. Cancer Lett 2010; 297:12636.
  • 41
    Anraku M, Tagawa T, Wu L, Yun Z, Keshavjee S, Zhang L, Johnston MR, de Perrot M. Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignant mesothelioma. J Immunol 2010; 185:95666.
  • 42
    Maas RA, Becker MJ, Weimar IS, De Nooy JC, Dullens HF, Den Otter WD. Transfer of tumor immunity by both CD4+ and CD8+ tumor infiltrating T lymphocytes activated in vivo by IL-2 therapy of tumor bearing mice. Immunobiology 1993; 188:28192.
  • 43
    Soruri A, Fayyazi A, Gieseler R, Schlott T, Runger TM, Neumann C, Peters JH. Specific autologous anti-melanoma T cell response in vitro using monocyte-derived dendritic cells. Immunobiology 1998; 198:52738.
  • 44
    Tatum AM, Mylin LM, Bender SJ, Fischer MA, Vigliotti BA, Tevethia MJ, Tevethia SS, Schell TD. CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumors. J Immunol 2008; 181:440617.
  • 45
    Umeshappa CS, Xiang J. Tumor-derived HLA-G1 acquisition by monocytes through trogocytosis: possible functional consequences. Cell Mol Life Sci 2010; 67:41078.
  • 46
    Badovinac VP, Haring JS, Harty JT. Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8+ T cell response to infection. Immunity 2007; 26:82741.
  • 47
    Sato Y, Shomura H, Maeda Y et al. Immunological evaluation of peptide vaccination for patients with gastric cancer based on pre-existing cellular response to peptide. Cancer Sci 2003; 94:8028.
  • 48
    Hunder NN, Wallen H, Cao J et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med 2008; 358:2698703.
  • 49
    Schmidt J, Neumann-Haefelin C, Altay T, Gostick E, Price DA, Lohmann V, Blum HE, Thimme R. Immunodominance of HLA-A2-restricted hepatitis C virus-specific CD8+ T cell responses is linked to naive-precursor frequency. J Virol 2011; 85:52326.
  • 50
    Kotturi MF, Scott I, Wolfe T et al. Naive precursor frequencies and MHC binding rather than the degree of epitope diversity shape CD8+ T cell immunodominance. J Immunol 2008; 181:212433.