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SUMMARY In a distribution line, power system control and power equipment investment are planned based on a measured power system current. However, recently the mass introduction of photovoltaic (PV) make it difficult for us to precisely measure the demand curve that is a current consumed by electrical equipment because the reversal power flow from PV systems is superposed. Therefore, the prediction of demand curves of distribution line is indispensable for power system management. In addition, it is also necessary to estimate the reliability of the predicted values as well as predicted current itself. In this paper, we propose the estimation method of the prediction interval that is the index of reliability based on the past demand curve database. The feature of the proposed method based on Just-In-Time (JIT) modeling make it possible for us to accurately estimate the prediction interval by the normalized database of demand curve. In this paper, some numerical examples are presented, which demonstrate the effectiveness of the proposed method.

Although T helper 17 (Th17) cells have been found in tumor tissues, their function in cancer immunity is unclear. We found that interleukin-17A (IL-17A)-deficient mice were more susceptible to developing lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the Th17 cells retained their cytokine signature and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 cells elicited a remarkable activation of tumor-specific CD8(+) T cells, which were necessary for the antitumor effect. Th17 cells promoted dendritic cell recruitment into the tumor tissues and in draining lymph nodes increased CD8 alpha(+) dendritic cells containing tumor material. Moreover, Th17 cells promoted CCL20 chemokine production by tumor tissues, and tumor-bearing CCR6-deficient mice did not respond to Th17 cell therapy. Thus, Th17 cells elicited a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. These findings have important implications in antitumor immunotherapies.

B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or down-modulate T-cell responses. Although it was shown that B7-H3 could inhibit T-cell responses, several studies - most of them performed in murine systems - found B7-H3 to act in a costimulatory manner. In this study, we have specifically addressed a potential functional dualism of human B7-H3 by assessing the effect of this molecule under varying experimental conditions as well as on different T-cell subsets. We show that B7-H3 does not costimulate human T cells. In the presence of strong activating signals, B7-H3 potently and consistently down-modulated human T-cell responses. This inhibitory effect was evident when analysing proliferation and cytokine production and affected naive as well as pre-activated T cells. Furthermore, we demonstrate that B7-H3-T-cell interaction is characterised by an early suppression of IL-2 and that T-cell inhibition can be reverted by exogenous IL-2. Since the triggering receptor expressed on myeloid cells like transcript 2 (TREML2/TLT-2) has been recently described as costimulatory receptor of murine B7-H3 we have extensively analysed interaction of human B7-H3 with TREML2/TLT-2. In these experiments we found no evidence for such an interaction. Furthermore, our data do not point to a role for murine TREML2 as a receptor for murine B7-H3.

Th17 and regulatory T (Treg) cells play opposite roles in autoimmune diseases. However, the mechanisms underlying their proper migration to inflammatory tissues are unclear. In this study, we report that these two T cell subsets both express CCR6. CCR6 expression in Th17 cells is regulated by TGF-β and requires two nuclear receptors, RORα and RORγ. Th17 cells also express the CCR6 ligand CCL20, which is induced synergistically by TGF-β and IL-6, which requires STAT3, RORγ and IL-21. Th17 cells, by producing CCL20, promote migration of Th17 and Treg cells in vitro in a CCR6-dependent manner. Lack of CCR6 in Th17 cells reduces the severity of experimental autoimmune encephalomyelitis and Th17 and Treg recruitment into inflammatory tissues. Similarly, CCR6 on Treg cells is also important for their recruitment into inflammatory tissues. Our data indicate an important role of CCR6 in Treg and Th17 cell migration.

B7-H3 is a new member of the B7 family. The receptor for B7-H3 has not been identified, but it seems to be expressed on activated T cells. Initial studies have shown that B7-H3 provides a stimulatory signal to T cells. However, recent studies suggest a negative regulatory role for B7-H3 in T cell responses. Thus, the immunological function of B7-H3 is controversial and unclear. In this study, we investigated the effects of neutralizing anti-B7-H3 mAb in a mouse model of allergic asthma to determine whether B7-H3 contributes to the development of pathogenic Th2 cells and pulmonary inflammation. Administration of anti-B7-H3 mAb significantly reduced airway hyperreactivity with a concomitant decrease in eosinophils in the lung as compared with control IgG-treated mice. Treatment with anti-B7-H3 mAb also resulted in decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the draining lymph node cells. Although blockade of B7-H3 during the induction phase abrogated the development of asthmatic responses, B7-H3 blockade during the effector phase did not inhibit asthmatic responses. These results indicated an important role for B7-H3 in the development of pathogenic Th2 cells during the induction phase in a murine model of asthma.

Dogfish (Squalus acanthias) growth hormone (GH) was identified by cDNA cloning and protein purification from the pituitary gland. Dogfish GH cDNA encoded a prehormone of 210 amino acids (aa). Sequence analysis of purified GH revealed that the prehormone is composed of a signal peptide of 27 aa and a mature protein of 183 aa. Dogfish GH showed 94% sequence identity with blue shark GH, and also showed 37-66%, 26%, and 48-67% sequence identity with GH from osteichtyes, an agnathan, and tetrapods. The site of production was identified through immunocytochemistry to be cells of the proximal pars distalis of the pituitary gland. Dogfish GH stimulates both insulin-like growth factor-I and II mRNA levels in dogfish liver in vitro. The dogfish GH gene consisted of five exons and four introns, the same as in lamprey, teleosts such as cypriniforms and siluriforms, and tetrapods. The 5'-flanking region within 1082 bp of the transcription start site contained consensus sequences for the TATA box, Pit-1/GHF-1, CRE, TRE, and ERE. These results show that the endocrine mechanism for growth stimulation by the GH-IGF axis was established at an early stage of vertebrate evolution, and that the 5-exon-type gene organization might reflect the structure of the ancestral gene for the GH gene family.

B7-H3 negatively regulates Th1-mediated immune responses. Here, we aimed to investigate whether B7-H3 is involved in the development of murine experimental allergic conjunctivitis (EC), which is predominantly mediated by Th2 cells. Intraperitoneal injection of anti-B7-H3 Ab during the induction phase of EC significantly augmented the severity of EC evaluated as conjunctival eosinophil numbers and Ag-induced IL-5 production by splenocytes. Injection of anti-B7-H3 Ab during the effector phase of EC did not significantly affect the severity of EC. In addition, transfer of Ag-primed splenocytes treated with anti-B7-H3 Ab in vitro did not significantly affect the severity of EC, compared to the splenocytes treated with the control Ab. Thus, regulation of EC by blocking of B7-H3 was observed during the induction phase but not the effector phase. Moreover, this study provides a new notion that B7-H3 regulates not only Th1-mediated but also Th2-mediated immune reactions.

Output of the photovoltaic (PV) system drastically fluctuates depending on weather conditions. Therefore users of PV systems should manage their energy usage with forecast information of the PV output. Due to the reasons above, we have developed an estimation method of X% prediction interval of solar irradiance. We have achieved a high-accuracy prediction interval for any prediction coefficient X%. However, we found that there are some errors in a case where the prediction coefficient is high. In this paper, we improve the estimation algorithm of the prediction interval.

Recently, for the purpose of utilizing renewable energy in a community, interactive electricity power networks, such as smart grid, have received much attention. In those electricity power networks, the technologies for maintain the balance of electricity demand and supply in a limited area become more important. Installing photovoltaic system can be effective for supplying electricity in a limited area at the peak load time, but PV output depends on weather conditions. Thus we propose to combine PV power generation with demand response program. We simulate interchange PV power with demand response program in a residential community. Some numerical results, which demonstrate the validity of the proposed method, will be presented.

ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4+ T cells in the region of the retina in EAU-induced mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN-gamma production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS-mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU.

PD-1 is an immunoinhibitory receptor that belongs to the CD28/CTLA-4 family. B7-H1 (PD-L1) and B7-DC (PD-L2), which belong to the B7 family, have been identified as ligands for PD-1. Paradoxically, it has been reported that both B7-H1 and B7-DC costimulate or inhibit T cell proliferation and cytokine production. To determine the role of B7-H1 and B7-DC in T cell-APC interactions, we examined the contribution of B7-H1 and B7-DC to CD4+ T cell activation by B cells, dendritic cells, and macrophages using anti-B7-H1, anti-B7-DC, and anti-PD-1 blocking mAbs. Anti-B7-H1 mAb and its Fab markedly inhibited the proliferation of anti-CD3-stimulated naive CD4+ T cells, but enhanced IL-2 and IFN-γ production in the presence of macrophages. The inhibition of T cell proliferation by anti-B7-H1 mAb was abolished by neutralizing anti-IFN-γ mAb. Coculture of CD4+ T cells and macrophages from IFN-γ-deficient or wild-type mice showed that CD4+ T cell-derived IFN-γ was mainly responsible for the inhibition of CD4+ T cell proliferation. Anti-B7-H1 mAb induced IFN-γ-mediated production of NO by macrophages, and inducible NO synthase inhibitors abrogated the inhibition of CD4+ T cell proliferation by anti-B7-H1 mAb. These results indicated that the inhibition of T cell proliferation by anti-B7-H1 mAb was due to enhanced IFN-γ production, which augmented NO production by macrophages, suggesting a critical role for B7-H1 on macrophages in regulating IFN-γ production by naive CD4+ T cells and, hence, NO production by macrophages.

Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten-induced contact hypersensitivity (CH). Administration of anti-PD-1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti-B7-H1 mAb, but not anti-B7-DC mAb, also enhanced CH reactions. The anti-PD-1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7-H1 was induced on activated T cells and antigen-presenting cells (APC) in the skin and the DLN, whereas B7-DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7-H1(+)B7-DC(-)CD86(low), was found in sensitized DLN. The blockade of B7-H1, but not B7-DC, dramatically enhanced the initial T cell proliferative responses against hapten-pulsed DLN APC, suggesting the preferential contribution of B7-H1 to the T cell-APC interaction. Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses.

Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in prediabetic female nonobese diabetic (NOD) mice regardless of age (from 1 to 10-wk-old), although it was most pronounced in the older mice. By contrast, cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade induced disease only in neonates. Male NOD mice also developed diabetes after PD-1–PD-L1 pathway blockade, but NOR mice, congenic to NOD but resistant to the development of diabetes, did not. Insulitis scores were significantly higher and frequency of interferon γ–producing GAD-reactive splenocytes was increased after PD-1–PD-L1 pathway blockade compared with controls. Interestingly, PD-L1 but not PD-L2 was found to be expressed on inflamed islets of NOD mice. These data demonstrate a central role for PD-1–PD-L1 interaction in the regulation of induction and progression of autoimmune diabetes in the NOD mouse and provide the rationale to develop new therapies to target this costimulatory pathway in this disease.

GH was identified in the sea lamprey, an extant representative of a group of the most ancient vertebrates, the Agnatha. A putative GH-cDNA was cloned from the pituitary by RT-PCR. The entire coding region comprised an open-reading frame of 203 amino acids (aa). The mature protein was also isolated from pituitaries, and fractionated by gel filtration and reverse-phase HPLC. A putative GH was monitored by Western blotting with a rabbit antiserum against a synthetic peptide corresponding to pre-GH sequence (aa 29-45). Sequence analysis of the purified protein demonstrated that the prehormone consists of a signal peptide of 22 aa and the mature protein of 181 aa, which shows 25% sequence identity with sturgeon GH. The site of production was identified through immunohistochemistry to be cells of the dorsal half of the proximal pars distalis of the pituitary. Following cDNA cloning of lamprey IGF cDNA, it was shown using RT-PCR that lamprey GH stimulates IGF expression in lamprey liver. This is the first study in which a member of the GH/prolactin/somatolactin family has been identified in an agnathan. In addition, GH appears to be the only member of this hormone family in the sea lamprey. Evidence suggests that GH is the ancestral hormone in the molecular evolution of the GH family and that the endocrine mechanism for growth stimulation was established at an early stage of vertebrate evolution.

Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently been identified as new members of the B7 family but their expression at the protein level remains largely unknown. To characterize the expression of B7-H1 and B7-DC, we newly generated an anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25). MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted. PD-1 was expressed on anti-CD3-stimulated T cells and anti-IgM plus anti-CD40-stimulated B cells at high levels but was undetectable on activated macrophages or DCs. B7-H1 was constitutively expressed on freshly isolated splenic T cells, B cells, macrophages, and dendritic cells (DCs), and up-regulated on T cells by anti-CD3 stimulation on macrophages by LPS, IFN-γ, GM-CSF, or IL-4, and on DCs by IFN-γ, GM-CSF, or IL-4. In contrast, B7-DC expression was only inducible on macrophages and DCs upon stimulation with IFN-γ, GM-CSF, or IL-4. The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation.

Various Invariant NKT (iNKT) cell ligands have been shown as potent adjuvants in boosting T cell reactivates to antigens on professional APC. Non-professional APC, such as T cells, also co-expressing MHC class I and CD1d, have been unattractive cell vaccine carriers due to their poor immunogenicity. Here, we report that T cells as well as T cell lymphoma can efficiently generate antigen-specific cytotoxic T lymphocytes (CTL) responses in mice in vivo, when formulated to present iNKT ligand α-galactosylceramide (αGC) on their surface CD1d. Vaccination with αGC-pulsed EG-7 T-cell lymphoma induced tumor-specific CTL response and suppressed the growth of EG-7 in a CD8 T cell-dependent manner. Injection of αGC-loaded CD4 T cells in mice efficiently activated iNKT cells in vivo. While T cells loaded with a class I-restricted peptide induced proliferation but not effector differentiation of antigen-specific CD8 T cells, injection of T cells co-pulsed with αGC strongly induced IFNγ and Granzyme B expression in T cells and complete lysis of target cells in vivo. Presentation of αGC and peptide on the same cells was required for optimal CTL response and vaccinating T cells appeared to directly stimulate both iNKT and cytotoxic CD8 T cells. Of note, the generation of this cytotoxic T cell response was independent of IL-4, IFNγ, IL-12, IL-21 and costimulation. Our data indicate that iNKT cell can license a non-professional APC to directly trigger antigen-specific cytotoxic T cell responses, which provides an alternative cellular vaccine strategy against tumors.

The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells. The putative receptor for BTNL1 was found on activated T cells and APCs. Also, recombinant BTNL1 molecule inhibited T cell proliferation by arresting cell cycle progression. The administration of neutralizing Abs against BTNL1 provoked enhanced T cell activation and exacerbated disease in autoimmune and asthma mouse models. Therefore, BTNL1 is a critical inhibitory molecule for T cell activation and immune diseases.

Activation-induced cell death (AICD) plays an important role in peripheral T-cell tolerance. AICD in CD4 T helper (Th) cells, including Th1 and Th2 effectors, has been extensively studied. Recently, interleukin-17–producing CD4+ T cells (Th17 cells) have been identified as a unique Th subset, but their susceptibility to AICD and the underlying molecular mechanisms have not been defined. In this study, we found that Th17 cells were significantly less susceptible to AICD than Th1 cells, and Th17 cell resistance to AICD is due to the high levels of c-Fas–associated death domain–like interleukin-1–converting enzyme inhibitory protein preventing Fas-mediated apoptosis. The resistance of Th17 cells to AICD reveals a novel mechanism to explain the high pathogenicity of Th17 cells in autoimmune diseases, and may also provide a rationale to generate tumor-specific Th17 cells for adoptive immunotherapy.

Although the protective functions by T helper 17 (Th17) cytokines against extracellular bacterial and fungal infection have been well documented, their importance against intracellular bacterial infection remains unclear. Here, we investigated the contribution of Th17 responses to host defense against intracellular bacteria Listeria monocytogenes and found that Th17 cell generation was suppressed in this model. Unexpectedly, mice lacking both p35 and EBI3 cleared L. monocytogenes as efficiently as wild-type mice, whereas p35-deficient mice failed to do so. Furthermore, both innate cells and pathogen-specific T cells from double-deficient mice produced significantly higher IL-17 and IL-22 compared to wild-type mice. The bacterial burden in the liver of double-deficient mice treated with anti-IL-17 was significantly increased compared to those receiving a control Ab. Transfer of Th17 cells specific for listeriolysin O as well as administration of IL-17 and IL-22 significantly suppressed bacterial growth in p35-deficient mice, indicating the critical contribution of Th17 responses to host defense against the intracellular pathogen in the absence of IL-12 and proper Th1 responses. Our findings unveil a novel immune evasion mechanism whereby the intracellular bacteria exploit IL-27EBI3 to suppress Th17-mediated protective immunity., Author Summary There is a considerable gap in our understanding of how pathogenic intracellular bacteria escape innate and adaptive host immunity. Production of IL-12, and subsequently IFNγ, upon infection triggers host immunity that prevents early dissemination of pathogenic intracellular pathogens. This is evident in observing the increased susceptibility of patients with deficiencies in IL-12, IFNγ, or their receptors to pathogenic intracellular bacteria such as Mycobacterium tuberculosis and Listeria monocytogenes (Lm). Paradoxically, the regulation of host defense by other members of the IL-12 family is poorly understood. Through the use of an animal model of Lm infection, we show that mice lacking IL-27EBI3 were resistant to Lm infection, even in the absence of IL-12. Neutralization and adoptive transfer studies showed that this protection was mediated through IL-17, IL-22 and Th17 responses. Thus our results identify IL-27EBI3 as a critical mechanism for immune escape by Lm in the absence of IL-12-mediated protective immunity. Furthermore, our work suggests that targeting IL-27EBI3 may represent a novel strategy for the treatment of bacterial infection in individuals lacking proper IL-12 responses.

Abstract 2648 Background: Programmed death (PD)-1, a coinhibitory receptor expressed by effector T cells (Teffs) is highly expressed on intratumoral T cells (mean 61%, range 34–86% for CD4+ T cells and mean 44%, range 31–69% for CD8+ T cells) in follicular lymphoma (FL), a finding associated with impaired ability to recognize autologous tumor (Nattamai et al, ASH 2007). Hence, PD-1 expression would be expected to confer an unfavorable prognosis in FL. However, correlation of PD-1 with clinical outcome in FL has been inconsistent with two studies showing favorable (Carreras et al, J Clin Oncol 2009; Wahlin et al, Clin Cancer Res 2010) and one study showing unfavorable (Richendollar et al, Hum Pathol 2011) outcome. While differences in method of analysis and type of treatment may explain the disparate results, a more complex model may be necessary to understand the prognostic impact of PD-1 in FL as PD-1 is expressed not only on antitumor Teffs but also on protumor follicular helper T cells (Tfh) and regulatory T cells (Tregs). Methods: To determine the nature of PD-1+ T cells in FL we performed comprehensive genomic and immunologic studies. By flow cytometry, we observed that the intratumoral CD4+ T cells in FL may be categorized into 3 subsets based on PD-1 expression - PD-1 high (PD-1hi), intermediate (PD-1int), and low (PD-1lo). The intratumoral CD8+ T cells consisted of PD-1int and PD-1lo subsets. The 3 CD4+ T cell subsets were FACSorted from FL tumors (n=3) and whole genome gene expression profiling (GEP) was performed. T cell subsets sorted similarly from tonsils served as controls for reactive follicular hyperplasia (FH) (n=3). Differentially expressed genes in GEP studies were confirmed at the mRNA level by real-time PCR (n=5) and at the protein level by flow cytometry when antibodies were available (n=5–10). Results: Our results suggested that CD4+PD-1hi T cells are Tfh cells (CXCR5hiBcl6hi ICOShiCD40LhiSAPhiPRDM1loIL-4hiIL-21hi); the CD4+PD-1int T cells consisted of a mixture of activated Teffs (CD45RO+CD45RA−) including Th1 (Tbet+IFNg+), Th2 (IL-10+), and Th17 cells (RORc+IL-17+), and Tregs (Foxp3+CD25hiCD127lo); and the CD4+PD-1lo T cells consisted of a mixture of activated Teffs (CD45RO+CD45RA− but IFNg−IL-4−IL-10−IL-17−), Tregs, and naïve T cells (CD45RO−CD45RA+CCR7+). Although these subsets were present in both FL and FH, there were important differences. IL-4 expression was significantly higher in Tfh in FL vs. FH and may play a role in the pathogenesis of FL. IL-17 expression was low and expression of coinhibitory molecules BTLA and CD200 was high in CD4+PD-1int T cells in FL vs. FH. BTLA and CD200 were also increased in CD8+PD-1int T cells in FL vs. FH. However, other coinhibitory molecules (LAG-3, Tim-3, CD160, CTLA-4, CD244, KLRG1) were not significantly different between FL and FH. CD4+PD-1int T cells also had higher expression of BATF, a transcription factor associated with T cell exhaustion in FL vs. FH. Together, these results suggest that the CD4+PD-1int T cells in FL may be in a state of T cell exhaustion whereas the CD4+PD-1int T cells in FH may represent recently activated Teffs. Consistent with this, blocking PD-1 with anti-PD-1 blocking antibody significantly enhanced proliferation and the production of Th1 (IFNg, TNFa) but not Th2 (IL-4, IL-5, IL-10, IL-13) cytokines by intratumoral CD4+ and CD8+ T cells in response to stimulation with autologous FL tumor cells (n=3). As expected, Tregs were increased in number in FL vs. FH and were present in the PD-1int and PD-1lo T cell subsets. We found 74% (range 40–97%) of FL Tregs expressed PD-1. Among the CD4+PD-1lo and CD8+PD-1lo T cells, there were more activated Teffs and fewer naïve T cells in FL vs. FH. Conclusions: Our results suggest that the PD-1+ T cells in FL are comprised of a mixture of antitumor Teffs and protumor Tfh and Tregs. The prognostic impact of PD-1+ T cells in FL may dependent on the relative frequency of these subsets as ligation of PD-1 may produce favorable (inhibition of protumor Tfh and Tregs) or unfavorable (inhibition of antitumor Teffs) outcomes by inhibiting or promoting tumor growth, respectively. Conversely, our results imply that agents that block PD-1/PD-ligand pathway may have the opposite effect on these T cell subsets and enumeration of the intratumoral PD-1+ T cell subsets may serve as biomarker to predict response to these agents in FL and possibly other B-cell malignancies. Disclosures: Dong: GSK: Consultancy; Genentech: Honoraria; Tempero: Consultancy; Ono: Consultancy; AnaptysBio: Consultancy. Neelapu:Cure Tech Ltd: Research Funding.