CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction.
We have assessed the functional effects of a panel of CTLA-4 mAbs on resting human CD4+ T cells. Our results demonstrate that some CTLA-4 mAbs can inhibit proliferative responses of resting CD4+ cells and cell cycle transition from G0 to G1. The inhibitory effects of CTLA-4 were evident within 4 h, at a time when cell surface CTLA-4 expression remained undetectable. Other CTLA-4 mAbs had no detectable inhibitory effects, indicating that binding of Ab to CTLA-4 alone is not sufficient to mediate down-regulation of T cell responses. Interestingly, while IL-2 production was shut off, inhibitory anti-CTLA-4 mAbs permitted induction and expression of the cell survival gene bcl-X(L). Consistent with this observation, cells remained viable and apoptosis was not detected after CTLA-4 ligation.
Blair
P J
PJ
Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Riley
J L
JL
Levine
B L
BL
Lee
K P
KP
Craighead
N
N
Francomano
T
T
Perfetto
S J
SJ
Gray
G S
GS
Carreno
B M
BM
June
C H
CH
D000069594:Abatacept; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D060908:CTLA-4 Antigen; D002453:Cell Cycle; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D051020:bcl-X Protein
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C494811:BCL2L1 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D000069594:Abatacept