Differential expression of CD28 and CD94/NKG2 on T cells with identical TCR beta variable regions in primary melanoma and sentinel lymph node.
NK cell tolerance is maintained by the interaction of killer inhibitory receptors with self MHC class I gene products. A subset of T cells also express killer inhibitory receptors, but the functional significance of this is unclear. Here we demonstrate that the expression of the C-lectin-like killer inhibitory receptor CD94 / NKG2 on T cells depends on the state of differentiation during the immune response to solid tumors. To this end we identified clonally expanded T cells which were present both in the sentinel lymph node of primary melanoma, as well as in the tumor itself. In situ characterization of such T cell clonotypes revealed that within the early stages of T cell activation, i. e. priming in the lymph node, T cells did not express CD94 / NKG2 whereas the same T cell clones expressed high levels of CD94 / NKG2 having reached the effector state at the tumor site. Moreover, while the phenotype of these T cell clones was CD28high in the lymph node only CD28low or CD28- T cells were found within the tumor. Double staining for CD94 and CD28 conformed that CD94 / NKG2-expressing cells were preferentially CD28-. Thus, T cells may down-regulate CD28 and up-regulate NK receptors as consequence of prolonged activation for cytolytic effector function. It is likely that NK receptors are involved in peripheral regulatory mechanisms avoiding overwhelming immune responses and immunopathology, particularly in situations of long-lasting immune activation.
Becker
J C
JC
Department of Dermatology, School of Medicine, W¿rzburg, Germany. becker-jc.derma@mail.uni-wuerzburg.de
Vetter
C S
CS
Schrama
D
D
Bröcker
E B
EB
thor Straten
P
P
D015703:Antigens, CD / Q000032:analysis*; D018106:CD28 Antigens / Q000032:analysis*; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000737:chemistry*; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000737:chemistry*
D015703:Antigens, CD; D018106:CD28 Antigens; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta