Functional Heterogeneity of Vaccine-Induced CD8 super(+) T Cells

• Published in: The Journal of immunology (1950) 2002-06, Vol.168 (11), p.5933-5942
• Main Authors: Monsurro, V, Nagorsen, D, Wang, E, Provenzano, M, Dudley, ME, Rosenberg, SA, Marincola, F M
• Format: Article
• Language: English
• ISSN: 0022-1767

The functional status of circulating vaccine-induced, tumor-specific T cells has been questioned to explain their paradoxical inability to inhibit tumor growth. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8 super(+) T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209 217(210 M) epitope. T cell precursor frequency increased from undetectable to 12,400 plus or minus 3,600 x 10 CD8 super(+) T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA super(+)CD27 super(+) (14 plus or minus 2.6% of tHLA-staining T cells), naive; CD45RA super(-)CD27 super(+) (14 plus or minus 3.2%), memory; CD45RA super(+)CD27 super(-) (43 plus or minus 6%), effector; and CD45RA super(-)CD27 super(-) (30 plus or minus 4.1%), memory/effector. The majority of tHLA super(+)CD8 super(+) T cells displayed an effector, CD27 super(-) phenotype (73%). However, few expressed perforin (17%). Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin super(+) (84 plus or minus 3.6%; by paired t test, p < 0.001) and CD27 super(+) (from 28 to 67%; by paired t test, p = 0.01) tHLA super(+) T cells. This conversion probably represented a change in the functional status of tHLA super(+) T cells rather than a preferential expansion of a CD27 super(+) (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA super(+)CD27 super(-)). These findings suggest that circulating vaccine-elicited T cells are not as functionally active as inferred by characterization of IVS-induced CTL. In addition, CD45RA/CD27 expression may be more informative about the status of activation of circulating T cells than their status of differentiation.