Evelyn Rodrigo | University of Maryland Baltimore (original) (raw)

Papers by Evelyn Rodrigo

Colored spots indicate the reaction of enzyme-labeled secondary antibodies against secreted IgG a... more Colored spots indicate the reaction of enzyme-labeled secondary antibodies against secreted IgG and represent one antibody-secreting cell. (B) Quantification of total IgG (top) and CYP2D6-specific IgG (bottom)–secreting cells per 10 splenocytes in FVB/N and CYP2D6 mice at the time points indicated. Note that B cells secreting CYP2D6 antibody–specific antibodies were only detectable after Ad-2D6 infection. ND, not detectable. (C) IgM and IgG type anti-CYP2D6 antibody generation in FVB/N and CYP2D6 mice infected with either Ad-2D6 or Ad-GFP over time. Data are mean ± SEM. (D) Representative pictures of rat liver sections stained with sera from Ad-2D6–infected CYP2D6 mice, Ad-2D6–infected FVB/N mice, AIH-1 patients (ANA), AIH-2 patients (LKM-1), and PBC patients (antimitochondrial antibodies), followed by Alexa Fluor 488–conjugated anti–mouse IgG or FITC-conjugated anti–human IgG secondary antibody. Bars, 50 μm.<b>Copyright information:</b>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"The Journal of Experimental Medicine 2008;205(6):1409-1422.Published online 9 Jun 2008PMCID:PMC2413037.

Bars, 50 μm. (B) Serum levels of ALT and AST in humanized CYP2D6 and wild-type FVB/N mice infecte... more Bars, 50 μm. (B) Serum levels of ALT and AST in humanized CYP2D6 and wild-type FVB/N mice infected with Ad-2D6 or Ad-GFP at several times after infection. Note that elevations in serum ALT and AST were transient and not persistent. Statistical evaluation ( test) revealed no significant differences in AST and ALT augmentation curves over time between Ad-2D6– and Ad-GFP–infected mice (FVB, P = 0.7 [ALT] and 0.79 [AST]; CYP2D6, P = 0.5 [ALT] and 0.13 [AST]) and between FVB/N and CYP2D6 mice (Ad-2D6, P = 0.64 [ALT] and 0.59 [AST]; Ad-GFP, P = 0.31 [ALT] and 0.82 [AST]). (C) Serum levels of AP in humanized CYP2D6 and wild-type FVB/N mice infected with Ad-2D6 or Ad-GFP at several times after infection ( = 5 per group). Transient AP elevation was detected in CYP2D6 and FVB/N mice at weeks 1 and 2 after infection with Ad-2D6 but not Ad-GFP. Statistical evaluation ( test) revealed significant differences in serum AP compared with preinfection levels (week 1, P = 0.035 [FVB/N Ad-2D6]; week 2, P = 0.044 [FVB/N Ad-2D6] 0.029 [CYP2D6 Ad-2D6]) and between Ad-2D6– and Ad-GFP–infected mice (week 1, P = 0.03 [FVB] and 0.063 [CYP2D6]; week 2, P = 0.055 [FVB] and 0.029 [CYP2D6]). Data are mean ± SD.<b>Copyright information:</b>Taken from "Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection"The Journal of Experimental Medicine 2008;205(6):1409-1422.Published online 9 Jun 2008PMCID:PMC2413037.

Cancer Research, Aug 15, 2020

Anti-PD1/L1 has become the backbone of immune therapy for many cancer types. However, the majorit... more Anti-PD1/L1 has become the backbone of immune therapy for many cancer types. However, the majority of patients do not respond due to a myriad of mechanisms affecting the tumor microenvironment, including low tumor mutational burden and low immune cell infiltrate. Innate immune agonists can potentially address both issues by increasing tumor antigen presentation and tumor microenvironment inflammation, thereby turning cold tumors hot. As clinical proof-of-concept, many intratumoral TLR/STING agonists have shown promising anti-tumor responses as single agents and in combination with checkpoint inhibitors; however, successful clinical applications have been limited to cutaneous-accessible tumor types. APR003 is an orally-administered GI/liver-targeted small molecule TLR7 agonist designed for the treatment of visceral colorectal and liver cancers. Studies in mice and monkeys demonstrate robust Type-1 Interferon pathway activation with good tolerability. APR003 is efficacious in several syngeneic orthotopic models of liver and colon cancer, both as single agent and in combination with anti-PDL1. Mechanistic studies show enhancement of CD103+ dendritic cells in tumor draining lymph nodes and tumor antigen-specific T cells in the tumor microenvironment. Pre-clinical pharmacology data will be presented. Citation Format: Andrew T. Miller, Evelyn Rodrigo, Manny Corpuz, David Plouffe, Tom Y.-H. Wu. Gastrointestinal/liver-targeted TLR7 agonist for treatment of colorectal and liver cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 684.

Hepatology communications, Jul 8, 2019

Current therapeutics for chronic infection with hepatitis B virus (HBV) rarely induce functional ... more Current therapeutics for chronic infection with hepatitis B virus (HBV) rarely induce functional cure due to the immunotolerant status of patients. Small molecule agonists targeting toll-like receptor 7 (TLR7) have been shown to elicit a functional cure in animal models of HBV but sometimes with poor tolerability due to immune-related toxicities. In an effort to increase the therapeutic window of TLR7 agonists to treat chronic hepatitis B (CHB), we developed an oral TLR7 agonist, APR002, designed to act locally in the gastrointestinal tract and liver, thus minimizing systemic exposure and improving tolerability. Here, we describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of APR002 in mice and uninfected woodchucks as well as the safety and antiviral efficacy in combination with entecavir (ETV) in woodchucks with CHB. Treatment of woodchucks chronically infected with woodchuck hepatitis virus (WHV) with weekly oral doses of APR002 was well-tolerated. While APR002 and ETV single agents did not elicit sustained viral control, combination therapy resulted in durable immune-mediated suppression of the chronic infection. These woodchucks also had detectable antibodies to viral antigens, enhanced interferonstimulated gene expression, and loss of WHV covalently closed circular DNA. Conclusion: APR002 is a novel TLR7 agonist exhibiting a distinct PK/PD profile that in combination with ETV can safely attain a functional cure in woodchucks with chronic WHV infection. Our results support further investigation of liver-targeted TLR7 agonists in human CHB. (Hepatology Communications 2019;0:1-15).

Journal of Experimental Medicine, Apr 19, 2004

The T-box transcription factor T-bet is known to control lineage commitment and interferon-␥ prod... more The T-box transcription factor T-bet is known to control lineage commitment and interferon-␥ production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter-lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-␥ , but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.

Diabetes, Nov 1, 2000

Autoimmune diabetes is caused by selective loss of insulin-producing pancreatic ␤-cells. The main... more Autoimmune diabetes is caused by selective loss of insulin-producing pancreatic ␤-cells. The main factors directly implicated in ␤-cell death are autoreactive, cytotoxic (islet-antigen specific) T-lymphocytes (CTL), and inflammatory cytokines. In this study, we have used an antigen-specific model of virally induced autoimmune diabetes to demonstrate that even high numbers of autoreactive CTL are unable to lyse ␤-cells by perforin unless major histocompatibility complex class I is upregulated on islets. This requires the presence of inflammatory cytokines induced by viral infection of the exocrine pancreas but not of the ␤-cells. Unexpectedly, we found that the resulting perforin-mediated killing of ␤-cells by autoreactive CTL is not sufficient to lead to clinically overt diabetes in vivo, and it is not an absolute prerequisite for the development of insulitis, as shown by studies in perforin-deficient transgenic mice. In turn, destruction of ␤-cells also requires a direct effect of ␥-interferon (IFN-␥), which is likely to be in synergy with other cytokines, as shown in double transgenic mice that express a mutated IFN-␥ receptor on their ␤-cells in addition to the viral (target) antigen and do not develop diabetes. Thus, destruction of most ␤-cells occurs as cytokine-mediated death and requires IFN-␥ in addition to perforin. Understanding these kinetics could be of high conceptual importance for the design of suitable interventions in prediabetic individuals at risk to develop type 1 diabetes.

Journal of Immunology, Jun 15, 2001

Functional impairment of regulatory T cell in multiple low dose streptozotocin induced murine dia... more Functional impairment of regulatory T cell in multiple low dose streptozotocin induced murine diabetes (P3099)

Cancer Research, Apr 4, 2023

Transforming growth factor beta (TGFβ) signaling has been implicated in many cancers and fibrotic... more Transforming growth factor beta (TGFβ) signaling has been implicated in many cancers and fibrotic diseases. Recent pharmacological intervention has shown promising activities in preclinical models and early clinical trials. There are over 15 investigational agents targeting this pathway currently in the clinic, but none have been approved. In particular, small molecule TGFβ inhibitors targeting ALK5 (TGFβ type 1 receptor) have been limited by mechanism-based heart valve toxicity to low dose and intermittent dosing regimens. NEX002 is an oral liver-targeted ALK5 inhibitor with low heart exposure for the treatment of liver cancer and other gastrointestinal cancers with liver metastases. The compound was designed following drug design principles from known liver-specific drugs, such as the statins. In animals, NEX002 exerts preferential distribution (pharmacokinetic) and target inhibition (pharmacodynamic) in liver over the heart. NEX002 has demonstrated activity in several intrahepatic and subcutaneous tumor models, and significantly enhanced the durability of anti-tumor efficacy in combination with lenvatinib, a VEGFR inhibitor approved for the treatment of hepatocellular carcinoma. No heart valve toxicity was observed when benchmarked against galunisertib (systemic ALK5 inhibitor) in toxicity studies with repeated daily dosing. These data suggest that our liver-targeted/heart-sparing approach may allow more robust target engagement compared to systemic ALK5 inhibitors through higher dose or more frequent dosing. Citation Format: Andrew T. Miller, Qihui Jin, David Plouffe, Manny Corpuz, Evelyn Rodrigo, Tom Y.- Wu. Heart-sparing ALK5 inhibitor for treatment of gastrointestinal and liver cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1661.

Journal of Clinical Investigation, 2004

Viruses can cause but can also prevent autoimmune disease. This dualism has certainly hampered at... more Viruses can cause but can also prevent autoimmune disease. This dualism has certainly hampered attempts to establish a causal relationship between viral infections and type 1 diabetes (T1D). To develop a better mechanistic understanding of how viruses can influence the development of autoimmune disease, we exposed prediabetic mice to various viral infections. We used the well-established NOD and transgenic RIP-LCMV models of autoimmune diabetes. In both cases, infection with the lymphocytic choriomeningitis virus (LCMV) completely abrogated the diabetic process. Interestingly, such therapeutic viral infections resulted in a rapid recruitment of T lymphocytes from the islet infiltrate to the pancreatic draining lymph node, where increased apoptosis was occurring. In both models this was associated with a selective and extensive expression of the chemokine IP-10 (CXCL10), which predominantly attracts activated T lymphocytes, in the pancreatic draining lymph node, and in RIP-LCMV mice it depended on the viral antigenic load. In RIP-LCMV mice, blockade of TNF-α or IFN-γ in vivo abolished the prevention of T1D. Thus, virally induced proinflammatory cytokines and chemokines can influence the ongoing autoaggressive process beneficially at the preclinical stage, if produced at the correct location, time, and levels.

Journal of Virology, May 15, 2003

Accurate control of the balance of the T1 and T2 cells during antiviral immunity is essential for... more Accurate control of the balance of the T1 and T2 cells during antiviral immunity is essential for optimizing immune effector functions and for avoiding potentially severe immunopathology. We examined the in vivo role of the signal transducer and activator of transcription (STAT) 4 in regulating the T1/T2 balance during the response to live influenza virus and isolated viral proteins. We found that the differentiation of gamma interferon (IFN-␥)-producing Th1 and Tc1 cells after inoculation of live virus occurred independently of STAT 4 expression. Influenza virus-specific T2 and Tc2 responses were well controlled in such STAT 4-deficient mice unless IFN-␥ was eliminated as well. In contrast, the STAT 4-dependent signaling pathway played a more essential role in regulating the T1/T2 balance after immunization with viral proteins and, in particular, inactivated nonreplicating virus. Pulmonary infection was cleared even in the absence of both functional STAT 4 genes and functional IFN-␥ genes because virus-neutralizing antibodies were still generated, consistent with a substantial redundancy in different antiviral effector pathways. Thus, replicating agents such as live influenza virus can elicit IFN-␥ and control T2 immunity independently of STAT 4, whereas the profile of immunity to isolated proteins is more reliant on an intact STAT 4 signaling pathway.

Clinical Immunology, 2007

Diabetes, Mar 1, 2004

Tissue-specific expression of Fas-ligand (Fas-L) can provide immune privilege by inducing apoptos... more Tissue-specific expression of Fas-ligand (Fas-L) can provide immune privilege by inducing apoptosis of "invading" lymphocytes expressing Fas. However, accelerated diabetes has been reported in transgenic mice expressing Fas-L in islets (RIP-Fas-L) as a result of Fas-dependent fratricide of ␤-cells after transfer of diabetogenic clones. Here we studied whether Fas-L could protect islets from autoaggressive CD8 lymphocytes in a transgenic model of virally induced diabetes (RIP-LCMV-NP transgenic mice), in which the autoaggressive response is directed to a viral nucleoprotein (NP) expressed as a transgene in ␤-cells. Indeed, disease incidence after viral (lymphocytic choriomeningitis virus [LCMV]) infection was reduced by ϳ30%, which was associated with a decrease of autoaggressive CD8 NP-specific lymphocytes in islets and pancreatic draining lymph nodes. However, surprisingly, a high degree (50%) of diabetes was seen in mice that expressed only Fas-L but not the viral transgene (NP) in ␤-cells after infection with LCMV. This was due to induction of Fas on ␤-cells after LCMV infection of the pancreas, resulting in Fas/Fas-L-mediated fratricide. Thus, although Fas-L can lend some immune privilege to islet cells, local virus-induced inflammation will induce Fas on ␤-cells, leading to their mutual destruction if Fas-L is present. Expression of Fas-L therefore might not be protective in situations in which viral inflammation can be expected, resulting in Fas induction on the targeted cell itself.

Journal of Virology, 2006

CTLA-4 is considered one of the most potent negative regulators of T-cell activation. To circumve... more CTLA-4 is considered one of the most potent negative regulators of T-cell activation. To circumvent experimental limitations due to fatal lymphoproliferative disease associated with genetic ablation of CTLA-4, we have used radiation chimeras reconstituted with a mixture of CTLA-4 ؉/؉ and CTLA-4 ؊/؊ bone marrow that retain a normal phenotype and allow the evaluation of long-term T-cell immunity under conditions of intrinsic CTLA-4 deficiency. Following virus infection, we profiled primary, memory, and secondary CD8 ؉ and CD4 ؉ T-cell responses directed against eight different viral epitopes. Our data demonstrate unaltered antigen-driven proliferation, acquisition of effector functions, distribution of epitope hierarchies, T-cell receptor repertoire selection, functional avidities, and long-term memory maintenance in the absence of CTLA-4. Moreover, regulation of memory T-cell survival and homeostatic proliferation, as well as secondary responses, was equivalent in virus-specific CTLA4 ؉/؉ and CTL-A-4 ؊/؊ T-cell populations. Thus, lack of CTLA-4 expression by antigen-specific T cells can be compensated for by extrinsic factors in the presence of CTLA-4 expression by other cells. These findings have implications for the physiologic, pathological, and therapeutic regulation of costimulation.

Malaria Journal, Sep 11, 2013

Background: One of the main causes of mortality from severe malaria in Plasmodium falciparum infe... more Background: One of the main causes of mortality from severe malaria in Plasmodium falciparum infections is cerebral malaria (CM). An important host genetic component determines the susceptibility of an individual to develop CM or to clear the infection and become semi-immune. As such, the identification of genetic loci associated with susceptibility or resistance may serve to modulate disease severity. Methodology: The Plasmodium berghei mouse model for experimental cerebral malaria (ECM) reproduces several disease symptoms seen in human CM, and two different phenotypes, a susceptible (FVB/NJ) and a resistant mouse strain (DBA/2J), were examined. Results: FVB/NJ mice died from infection within ten days, whereas DBA/2J mice showed a gender bias: males survived on average nineteen days and females either died early with signs of ECM or survived for up to three weeks. A comparison of brain pathology between FVB/NJ and DBA/2J showed no major differences with regard to brain haemorrhages or the number of parasites and CD3+ cells in the microvasculature. However, significant differences were found in the peripheral blood of infected mice: For example resistant DBA/2J mice had significantly higher numbers of circulating basophils than did FVB/NJ mice on day seven. Analysis of the F2 offspring from a cross of DBA/2J and FVB/NJ mice mapped the genetic locus of the underlying survival trait to chromosome 9 with a Lod score of 4.9. This locus overlaps with two previously identified resistance loci (char1 and pymr) from a blood stage malaria model. Conclusions: Survival best distinguishes malaria infections between FVB/NJ and DBA/2J mice. The importance of char1 and pymr on chromosome 9 in malaria resistance to P. berghei was confirmed. In addition there was an association of basophil numbers with survival.

Clinical Immunology, 2007

Folic acid receptor 1 (FOLR1, FRα) is highly expressed in 80% of ovarian tumors and has a low nan... more Folic acid receptor 1 (FOLR1, FRα) is highly expressed in 80% of ovarian tumors and has a low nanomolar affinity for folic acid. Although ovarian tumors are intrinsically immunogenic, immune reactions to them are inhibited by a suppressive environment. We are developing a bispecific anti-CD3-folate to redirect T cells to engage with and kill tumor cells. Folic acid was site-specifically conjugated to a FAb fragment of an anti-CD3 antibody through an engineered linkable non-natural amino acid. Anti-CD3-folate bispecific FAb is able to engage T cells and exert cytotoxicity in a variety of tumor cell lines including ovarian; OV-90, OVCAR3, and breast cancer; SKOV-3. Cytotoxicity assays generated EC50 in the femtomolar range. This cytotoxicity could be modulated by varying folic acid concentrations in the assay medium. T-cell activation was confirmed by appearance of activation markers on the cell surface and secretion of pro-inflammatory cytokines after treatment of tumor cells in combination with human PBMC's. T cell activation and subsequent cytokine release is dependent on simultaneous binding of tumor and T cell to anti-CD3-Folate. In a xenograft mouse model of ovarian cancer, anti-CD3-folate significantly inhibited tumor growth, and increased life span (ILS)of 30% and 50% for SKOV-3 and OV-90, respectively when compared to control treated animals. These data suggest that anti-CD3-folate bispecifc FAb- mediated T cell engagement could be a powerful tool for immune-ablation of ovarian cancer. Citation Format: Jinming Xia, Kristine deDios, Evelyn Rodrigo, Robin Humphreys, Alan Wahl, Marco Gymnopoulos. Bispecific anti-CD3-folate for the treatment of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A58.

Journal of Virology, 2005

CTLA-4 is considered one of the most potent negative regulators of T-cell activation. To circumve... more CTLA-4 is considered one of the most potent negative regulators of T-cell activation. To circumvent experimental limitations due to fatal lymphoproliferative disease associated with genetic ablation of CTLA-4, we have used radiation chimeras reconstituted with a mixture of CTLA-4 +/+ and CTLA-4 −/− bone marrow that retain a normal phenotype and allow the evaluation of long-term T-cell immunity under conditions of intrinsic CTLA-4 deficiency. Following virus infection, we profiled primary, memory, and secondary CD8 + and CD4 + T-cell responses directed against eight different viral epitopes. Our data demonstrate unaltered antigen-driven proliferation, acquisition of effector functions, distribution of epitope hierarchies, T-cell receptor repertoire selection, functional avidities, and long-term memory maintenance in the absence of CTLA-4. Moreover, regulation of memory T-cell survival and homeostatic proliferation, as well as secondary responses, was equivalent in virus-specific CTLA...

The Journal of Immunology, 2005

During inflammation, chemokines are conductors of lymphocyte trafficking. The chemokine CXCL10 is... more During inflammation, chemokines are conductors of lymphocyte trafficking. The chemokine CXCL10 is expressed early after virus infection. In a virus-induced mouse model for type 1 diabetes, CXCL10 blockade abrogated disease by interfering with trafficking of autoaggressive lymphocytes to the pancreas. We have generated transgenic rat insulin promotor (RIP)-CXCL10 mice expressing CXCL10 in the β cells of the islets of Langerhans to evaluate how bystander inflammation influences autoimmunity. RIP-CXCL10 mice have islet infiltrations by mononuclear cells and limited impairment of β cell function, but not spontaneous diabetes. RIP-CXCL10 mice crossed to RIP-nucleoprotein (NP) mice expressing the NP of the lymphocytic choriomeningitis virus in the β cells had massively accelerated type 1 diabetes after lymphocytic choriomeningitis virus infection. Mechanistically, we found a drastic increase in NP-specific, autoaggressive CD8 T cells in the pancreas after infection. In situ staining with ...

The Journal of Immunology, 2001

We report here that islet-specific expression of TNF-α can play a dual role in autoimmune diabete... more We report here that islet-specific expression of TNF-α can play a dual role in autoimmune diabetes, depending on its precise timing in relation to the ongoing autoimmune process. In a transgenic model (rat insulin promoter-lymphocytic choriomeningitis virus) of virally induced diabetes, TNF-α enhanced disease incidence when induced through an islet-specific tetracycline-dependent promoter system early during pathogenesis. Blockade of TNF-α during this phase prevented diabetes completely, suggesting its pathogenetic importance early in disease development. In contrast, TNF-α expression abrogated the autoimmune process when induced late, which was associated with a reduction of autoreactive CD8 lymphocytes in islets and their lytic activities. Thus, the fine-tuned kinetics of an autoreactive process undergo distinct stages that respond in a differential way to the presence of TNF-α. This observation has importance for understanding the complex role of inflammatory cytokines in autoimm...

Cancer Research, Aug 15, 2020

Hepatology communications, Jul 8, 2019

Journal of Experimental Medicine, Apr 19, 2004

Diabetes, Nov 1, 2000

Journal of Immunology, Jun 15, 2001

Cancer Research, Apr 4, 2023

Journal of Clinical Investigation, 2004

Journal of Virology, May 15, 2003

Clinical Immunology, 2007

Diabetes, Mar 1, 2004

Journal of Virology, 2006

Malaria Journal, Sep 11, 2013

Clinical Immunology, 2007

Journal of Virology, 2005

CTLA-4 is considered one of the most potent negative regulators of T-cell activation. To circumve... more CTLA-4 is considered one of the most potent negative regulators of T-cell activation. To circumvent experimental limitations due to fatal lymphoproliferative disease associated with genetic ablation of CTLA-4, we have used radiation chimeras reconstituted with a mixture of CTLA-4 +/+ and CTLA-4 −/− bone marrow that retain a normal phenotype and allow the evaluation of long-term T-cell immunity under conditions of intrinsic CTLA-4 deficiency. Following virus infection, we profiled primary, memory, and secondary CD8 + and CD4 + T-cell responses directed against eight different viral epitopes. Our data demonstrate unaltered antigen-driven proliferation, acquisition of effector functions, distribution of epitope hierarchies, T-cell receptor repertoire selection, functional avidities, and long-term memory maintenance in the absence of CTLA-4. Moreover, regulation of memory T-cell survival and homeostatic proliferation, as well as secondary responses, was equivalent in virus-specific CTLA...

The Journal of Immunology, 2005

The Journal of Immunology, 2001