Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs islet allograft survival

Wayne Truong; Jennifer C. Plester; Wayne W. Hancock; Jonathan Kaye; Shaheed Merani; Kenneth M. Murphy; Theresa L. Murphy; Colin C. Anderson; A. M.James Shapiro

doi:10.1097/01.tp.0000289995.70390.20

Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs islet allograft survival

Wayne Truong, Jennifer C. Plester, Wayne W. Hancock, Jonathan Kaye, Shaheed Merani, Kenneth M. Murphy, Theresa L. Murphy, Colin C. Anderson, A. M.James Shapiro

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been implicated in the regulation of autoimmune and may potentially play a role in alloimmune responses. An anti-BTLA monoclonal antibody has been reported to prolong fully major histocompatibility complex-mismatched cardiac allograft survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig) costimulatory blockade in islet transplantation. We investigated the potential of PJ196, and show that it did not deplete BTLA expressing cells, but it caused down-regulation of BTLA on the surface of lymphocytes and accumulation of cells with regulatory phenotype at the graft site, promoting islet allograft acceptance together with CTLA4Ig. The combination of BTLA coinhibitory modulation and CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for inducing long-term allograft survival.

Original language	English
Pages (from-to)	1368-1372
Number of pages	5
Journal	Transplantation
Volume	84
Issue number	10
DOIs	https://doi.org/10.1097/01.tp.0000289995.70390.20
State	Published - Nov 2007

Keywords

Coinhibition
Costimulatory blockade
Islet transplantation
Monoclonal antibody
Regulatory T cells
Tolerance

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10.1097/01.tp.0000289995.70390.20

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title = "Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs islet allograft survival",

abstract = "The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been implicated in the regulation of autoimmune and may potentially play a role in alloimmune responses. An anti-BTLA monoclonal antibody has been reported to prolong fully major histocompatibility complex-mismatched cardiac allograft survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig) costimulatory blockade in islet transplantation. We investigated the potential of PJ196, and show that it did not deplete BTLA expressing cells, but it caused down-regulation of BTLA on the surface of lymphocytes and accumulation of cells with regulatory phenotype at the graft site, promoting islet allograft acceptance together with CTLA4Ig. The combination of BTLA coinhibitory modulation and CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for inducing long-term allograft survival.",

keywords = "Coinhibition, Costimulatory blockade, Islet transplantation, Monoclonal antibody, Regulatory T cells, Tolerance",

author = "Wayne Truong and Plester, {Jennifer C.} and Hancock, {Wayne W.} and Jonathan Kaye and Shaheed Merani and Murphy, {Kenneth M.} and Murphy, {Theresa L.} and Anderson, {Colin C.} and Shapiro, {A. M.James}",

year = "2007",

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AU - Truong, Wayne

AU - Plester, Jennifer C.

AU - Hancock, Wayne W.

AU - Kaye, Jonathan

AU - Merani, Shaheed

AU - Murphy, Kenneth M.

AU - Murphy, Theresa L.

AU - Anderson, Colin C.

AU - Shapiro, A. M.James

PY - 2007/11

Y1 - 2007/11

N2 - The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been implicated in the regulation of autoimmune and may potentially play a role in alloimmune responses. An anti-BTLA monoclonal antibody has been reported to prolong fully major histocompatibility complex-mismatched cardiac allograft survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig) costimulatory blockade in islet transplantation. We investigated the potential of PJ196, and show that it did not deplete BTLA expressing cells, but it caused down-regulation of BTLA on the surface of lymphocytes and accumulation of cells with regulatory phenotype at the graft site, promoting islet allograft acceptance together with CTLA4Ig. The combination of BTLA coinhibitory modulation and CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for inducing long-term allograft survival.

AB - The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been implicated in the regulation of autoimmune and may potentially play a role in alloimmune responses. An anti-BTLA monoclonal antibody has been reported to prolong fully major histocompatibility complex-mismatched cardiac allograft survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig) costimulatory blockade in islet transplantation. We investigated the potential of PJ196, and show that it did not deplete BTLA expressing cells, but it caused down-regulation of BTLA on the surface of lymphocytes and accumulation of cells with regulatory phenotype at the graft site, promoting islet allograft acceptance together with CTLA4Ig. The combination of BTLA coinhibitory modulation and CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for inducing long-term allograft survival.

KW - Coinhibition

KW - Costimulatory blockade

KW - Islet transplantation

KW - Monoclonal antibody

KW - Regulatory T cells

KW - Tolerance

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AN - SCOPUS:38349098127

SN - 0041-1337

VL - 84

SP - 1368

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JO - Transplantation

JF - Transplantation

IS - 10

ER -

Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs islet allograft survival

Abstract

Keywords

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