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

M. B. Nielsen, V. Monsurro, S. A. Migueles, E. Wang, A. Perez-Diez, H. Lee, U. Kammula, S. A. Rosenberg, F. M. Marincola

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Abstract

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-γ 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-γ 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.

Original languageEnglish
Pages (from-to)2287-2296
Number of pages10
JournalJournal of Immunology
Volume165
Issue number4
Publication statusPublished - 15 Aug 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Nielsen, M. B., Monsurro, V., Migueles, S. A., Wang, E., Perez-Diez, A., Lee, H., Kammula, U., Rosenberg, S. A., & Marincola, F. M. (2000). Status of activation of circulating vaccine-elicited CD8+ T cells. Journal of Immunology, 165(4), 2287-2296.