TY - JOUR
T1 - Functional heterogeneity of vaccine-induced CD8+ T cells
AU - Monsurrò, Vladia
AU - Nagorsen, Dirk
AU - Wang, Ena
AU - Provenzano, Maurizio
AU - Dudley, Mark E.
AU - Rosenberg, Steven A.
AU - Marincola, Francesco M.
PY - 2002/6/1
Y1 - 2002/6/1
N2 - 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+ 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 ± 3,600 × 106 CD8+ T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA+CD27+ (14 ± 2.6% of tHLA-staining T cells), naive; CD45RA-CD27+ (14 ± 3.2%), memory; CD45RA+CD27- (43 ± 6%), effector; and CD45RA-CD27- (30 ± 4.1%), memory/effector. The majority of tHLA+CD8+ T cells displayed an effector, CD27- 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+ (84 ± 3.6%; by paired t test, p < 0.001) and CD27+ (from 28 to 67%; by paired t test, p = 0.01) tHLA+ T cells. This conversion probably represented a change in the functional status of tHLA+ T cells rather than a preferential expansion of a CD27+ (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA+CD27-). 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.
AB - 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+ 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 ± 3,600 × 106 CD8+ T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA+CD27+ (14 ± 2.6% of tHLA-staining T cells), naive; CD45RA-CD27+ (14 ± 3.2%), memory; CD45RA+CD27- (43 ± 6%), effector; and CD45RA-CD27- (30 ± 4.1%), memory/effector. The majority of tHLA+CD8+ T cells displayed an effector, CD27- 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+ (84 ± 3.6%; by paired t test, p < 0.001) and CD27+ (from 28 to 67%; by paired t test, p = 0.01) tHLA+ T cells. This conversion probably represented a change in the functional status of tHLA+ T cells rather than a preferential expansion of a CD27+ (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA+CD27-). 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.
UR - http://www.scopus.com/inward/record.url?scp=0036604134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036604134&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.168.11.5933
DO - 10.4049/jimmunol.168.11.5933
M3 - Article
C2 - 12023400
AN - SCOPUS:0036604134
SN - 0022-1767
VL - 168
SP - 5933
EP - 5942
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -