TY - JOUR
T1 - Self-specific CD8+ T cells maintain a semi-naive state following lymphopenia-induced proliferation
AU - Johnson, Lisa D.S.
AU - Jameson, Stephen C.
PY - 2010/5/15
Y1 - 2010/5/15
N2 - Upon transfer into T cell-deficient hosts, naive CD8+ T cells typically undergo lymphopenia-induced proliferation (LIP, also called homeostatic proliferation) and develop the phenotypic and functional characteristics of memory CD8+ T cells. However, the capacity of T cells with self-peptide/MHC specificity to respond in this way has not been intensively studied. We examined pmel-1 TCR transgenic CD8+ T cells that are specific for an epitope from gp100, a protein expressed by melanoma cells and normal melanocytes. Despite their self-specificity, naive pmel-1 cells were inefficient at LIP in typical lymphopenic hosts. In CD132 (common γ-chain)-deficient hosts, pmel-1 CD8+ T cells underwent extensive proliferation, but, surprisingly, the majority of these cells retained certain naive phenotypic traits (CD44low, CD122low) rather than acquiring the expected central-memory phenotype. Following LIP, pmel-1 T cells acquired the capacity to control B16F10 tumor growth, but only in common γ-chain- deficient host mice. Together, these data suggest that LIP does not always favor expansion of self-specific CD8 T cells and that sustained extensive lymphopenia is required for such cells to exhibit tumor control.
AB - Upon transfer into T cell-deficient hosts, naive CD8+ T cells typically undergo lymphopenia-induced proliferation (LIP, also called homeostatic proliferation) and develop the phenotypic and functional characteristics of memory CD8+ T cells. However, the capacity of T cells with self-peptide/MHC specificity to respond in this way has not been intensively studied. We examined pmel-1 TCR transgenic CD8+ T cells that are specific for an epitope from gp100, a protein expressed by melanoma cells and normal melanocytes. Despite their self-specificity, naive pmel-1 cells were inefficient at LIP in typical lymphopenic hosts. In CD132 (common γ-chain)-deficient hosts, pmel-1 CD8+ T cells underwent extensive proliferation, but, surprisingly, the majority of these cells retained certain naive phenotypic traits (CD44low, CD122low) rather than acquiring the expected central-memory phenotype. Following LIP, pmel-1 T cells acquired the capacity to control B16F10 tumor growth, but only in common γ-chain- deficient host mice. Together, these data suggest that LIP does not always favor expansion of self-specific CD8 T cells and that sustained extensive lymphopenia is required for such cells to exhibit tumor control.
UR - http://www.scopus.com/inward/record.url?scp=77954699492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954699492&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1000109
DO - 10.4049/jimmunol.1000109
M3 - Article
C2 - 20393139
AN - SCOPUS:77954699492
SN - 0022-1767
VL - 184
SP - 5604
EP - 5611
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -