Status of activation of circulating vaccine-elicited CD8+ T cells

被引:96
作者
Nielsen, MB
Monsurro, V
Migueles, SA
Wang, E
Perez-Diez, A
Lee, KH
Kammula, U
Rosenberg, SA
Marincola, FM
机构
[1] NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA
[2] NIAID, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA
[3] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.4049/jimmunol.165.4.2287
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Selective blunting of the status of activation of circulating tumor-specific T cells was invoked to explain their paradoxical coexistence with unhampered tumor growth. By analogy, lack of tumor regression in the face of observable melanoma vaccine-induced T cell responses might be attributed to their status of activation. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited T cell precursor frequency directly in PBMC of patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope (g209-2 M), Furthermore, we tested by intracellular (IC)-FACS analysis and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to produce cytokine in response to challenge with vaccine-related epitopes or vaccine-matched (HLA-A*0201) melanoma cells. Vaccine-induced enhancement of T cell precursor frequency could be detected with tHLA in PBMC from six of eight patients studied at frequencies ranging between 0.3 and 2.3% of the total CD8(+) population, Stimulation with vaccine-related epitopes induced IFN-gamma expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of these patients. Furthermore, down-regulation of tHLA staining was noted upon cognate stimulation that could be utilized as an additional marker of T cell responsiveness. Finally, we observed in six patients an enhancement of reactivity against vaccine-matched tumor targets that was partly independent of documented vaccine-specific immune responses. A strong correlation was noted between tHLA staining of postvaccination PBMC and IFN-gamma expression by the same samples upon vaccine-relevant stimulation and assessed either by IC-FACS or qRT-PCR, Thus, blunting of the status of T cell activation on itself cannot easily explain the lack of clinical responses observed with vaccination.
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收藏
页码:2287 / 2296
页数:10
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