| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The programmed death of T lymphocytes in the early stage of LM infection is independent of signaling through Fas, TNF, and IFN-
receptors (7) and thus differs from classical activation-induced cell death (AICD) (8). AICD is responsible for the elimination of Ag-specific effector cells at the end of an immune response (the contraction phase). AICD is also involved in depletion of Ag-specific T cells during infections by immunosuppressive agents, resulting in an ineffective response unable to control the primary infection and/or impaired immunity to reinfection (9, 10, 11). In contrast, the early T cell depletion during listeriosis does not appear to inhibit Ag-specific T cell responses and protective immunity (4, 5). Instead, the early massive T cell depletion occurs just before and during the initial generation of T cells that mediate protective immunity. These observations have led to the hypothesis that a nonfunctional subpopulation of T cells is selectively depleted (4, 5). However, the validity of this hypothesis and the nature of the nonfunctional subpopulation remain unknown.
Attrition of bystander memory T cells following heterologous viral infections has been well documented (3, 12, 13). Recent studies have also shown extensive depletion of bystander naive T cells during the early stage of viral infection (3). However, it is not known whether depletion involves exclusively bystander T cells or includes both Ag-specific and nonspecific T cells. The significance of bystander T cell depletion remains unknown and puzzling in the case of memory T cells, since it results in waning CD8 T cell memory and protective immunity.
In this study we show that most T cells, regardless of specificity, became activated to express early activation markers soon after LM infection. This was followed by selective depletion of nonspecific cells and massive expansion of Ag-specific T cells. Confocal microscopy demonstrated that the depletion was due to in situ death of nonspecific T cells. This phenomenon of early T cell activation and subsequent depletion of nonspecific T cells was also observed following LCMV infection. These results suggest that proinflammatory infections induce early T cell activation that sensitizes them to respond to Ags quickly or to die if they are not rescued by antigenic stimulation. Depletion of numerous bystander T cells at the early stage of infection may function to allow for maximal expansion of the Ag-specific T cell population.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
C57BL/6 mice (Thy1.2) were purchased from the National Cancer Institute (Frederick, MD). C57BL/6 (Thy1.1), P14, and OT-I TCR transgenic mice (14, 15) on B6.Thy1.1, B6.Thy1.2, and B6.Thy1.1/Thy1.2 backgrounds were bred in-house. All mice were maintained in institutional animal care and use committee-approved facilities at the University of Pennsylvania School of Medicine (Philadelphia, PA). Mice were age- and sex-matched within each experiment. Recombinant LM strains, rLM-gp33 and rLM-OVA, which express the H-2Db-restricted gp33–41 epitope of lymphocytic choriomeningitis virus (LCMV) and the H-2Db-restricted OVA epitope, OVA323–339, respectively, were constructed by chromosomal integration into wild-type strain 10403s (16, 17). Mice were infected i.v. with 
5 x 104 CFU LM or i.p. with 5 x 106 PFU of LCMV Armstrong strain (18).
Adoptive transfers
Splenocytes were isolated from P14 or OT-I mice and labeled with 5 µM CFSE (Molecular Probes, Eugene, OR) in PBS, then quenched with 100% FCS. Cells were then washed with RPMI 1640/10% FCS and resuspended in PBS. P14 and OT-I T cells were purified by MACS using CD8a Microbeads (Miltenyi Biotec, Bergisch Gladbach, Germany) and were transferred i.v. into recipient mice (2–5 x 106 cells/mouse, or 1–2 x 107 cells/mouse for confocal microscopy). For cotransfer experiments, equal numbers of purified CFSE-labeled P14 and OT-I cells were mixed and transferred. One day after transfer, recipients were infected with LM or LCMV.
Flow cytometry
Single-cell suspensions of splenocytes were resuspended in PBS/1% BSA/0.1% NaN3 at a concentration of 1–5 x 107 cells/ml, stained for cell surface markers using mAbs from BD PharMingen (San Diego, CA), and fixed with 2% paraformaldehyde/PBS. Flow cytometry was performed with a FACSCalibur (BD Biosciences, San Jose, CA), and data were analyzed using FlowJo software (Tree Star, San Carlos, CA).
In situ detection of apoptotic cells in spleens using TUNEL
Frozen 5-µm-thick spleen sections were fixed with 4% paraformaldehyde and permeabilized with 0.1% Triton X-100 in 0.1% sodium citrate. TUNEL-positive cells were detected using the In Situ Cell Death Detection Kit/TMR Red (Roche, Indianapolis, IN). Sections were viewed and photographed using a laser-scanning confocal fluorescence microscope system (1024-ES; Bio-Rad, Hercules, CA).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
To examine the early events of T cell response, we infected C57BL/6 mice with LM and followed the kinetics of activation and expansion of CD4 and CD8 T cells (Fig. 1). As reported by others (1, 4, 5, 6, 7), substantial depletion of T cells was evident by day 3 post-LM infection. The CD4 T cell population decreased from 8.5 x 106/spleen (23% of splenocytes) on day 0 to 2.6 x 106/spleen (11% of splenocytes) on day 3 after infection. Similarly, the CD8 T cell population decreased from 5 x 106/spleen (15% of splenocytes) on day 0 to 1.8 x 106/spleen (7% of splenocytes) on day 3. Beginning from day 3, however, both CD4 and CD8 T cell populations rebounded, and by day 7, CD4 and CD8 T cells reached 8.1 x 106/spleen (21% of splenocytes) and 8.5 x 106/spleen (32% of splenocytes), respectively. The increase in CD4 and CD8 T cells from days 3–7 was exclusively due to accumulation of activated (CD44high) cells. CD44high cells made up only 13% of CD8 cells on day 3, but increased to 81% on day 7 after infection (Fig. 1B), and a similar increase in the CD44high population was observed for CD4 T cells (data not shown). Thus, T cell compartments were repopulated from days 3–7 by activated T cells, which made up the majority of the T cell population at the peak of response on day 7.
|
To determine whether most of the activated T cells are specific to LM Ags or there is a substantial bystander activation of nonspecific T cells, we employed an adoptive transfer model using P14 TCR transgenic cells that are specific to the H-2Db-restricted gp33–41 epitope of LCMV. Before transfer, P14 cells were labeled with CFSE, a vital fluorescent dye that is equally partitioned into daughter cells, thus allowing visualization of cell division. Recipient mice were infected with a recombinant LM strain (rLM-gp33) that expresses the gp33–41 epitope or, as a control, the parental wild-type strain of LM (wtLM). On day 3 postinfection we examined the proliferation of P14 cells by analyzing CFSE profiles and determined their activation status by staining for CD62L, a surface marker whose expression is down-regulated in activated T cells. As expected, the transferred P14 cells became activated and proliferated rapidly in response to rLM-gp33 infection, while few, if any, P14 cells divided or displayed an activation phenotype in PBS-treated or wtLM-infected mice (Fig. 2A). Surprisingly, however, a substantial loss of P14 cells was noted in the wtLM-infected mice. Transferred P14 cells constituted 0.22% of the total splenocytes, which dropped to only 0.03% in wtLM-infected mice by day 3 postinfection. The total numbers of P14 cells per spleen were significantly lower in wtLM-infected (5 x 103) compared with PBS-treated (1 x 105) mice. Thus, >90% of transferred P14 cells were depleted in the spleens of wtLM-infected mice. In contrast, the P14 cells expanded >10-fold, to 2 x 106/spleen by day 3 in rLM-gp33 infected mice. These results indicate that gp33-specific P14 cells proliferated rapidly in response to rLM-gp33 infection, but were depleted in the spleen of wtLM-infected mice.
|
It is possible that depletion of Ag-specific cells also occurs but is accompanied or followed by Ag-driven expansion, resulting in an increase in total P14 cells despite their depletion. We thus took a quantitative approach to assess possible depletion of P14 cells in rLM-gp33 infected mice. We closely followed the proliferation of transferred, CFSE-labeled P14 cells at different time points after infection (Fig. 3). In wtLM-infected mice, there was no sign of P14 cells dividing before their depletion, which occurred between 36–48 h, resulting in >90% reduction of P14 cells by 48 h (Fig. 3, A and B). In rLM-gp33 infected mice there was no loss of P14 cells before their recruitment into division (0–36 h). By 48 h more P14 cells were present as a result of their proliferation, which gave rise to many daughter cells in successive divisions, as evident by their distinct peaks of CFSE fluorescence (Fig. 3A). To determine whether there was loss of P14 cells during proliferation, we deduced the number of original P14 cells (precursors) required to generate these daughter cells as previously described (19). If some P14 cells were lost during proliferation, the sum of the deduced number of precursors should be fewer than the number of P14 cells in PBS-treated control mice. However, our calculations revealed that the number of deduced P14 precursors in rLM-gp33 infected mice was not significantly different from that in PBS-treated control mice (Fig. 3C). Therefore, there was marginal loss of gp33-specific CD8 T cells in rLM-gp33-infected mice before and during the early phase of their expansion.
|
Early T cell depletion in the spleen of LM-infected mice may be explained by two possible mechanisms: altered trafficking or cell death. Previous studies have examined the possibility of altered trafficking as a potential mechanism, but found no supporting evidence (1, 6, 7). Lymphocyte depletion during the early stage of LM infection was observed in many organs (1, 7), and no redistribution of radiolabeled T cells from spleens into other organs was evident following LM infection (4). In light of our new findings, it is possible that Ag-specific T cells might be selectively retained in the spleen to respond to antigenic stimulation, while nonspecific T cells migrate out of spleen into other organs. We examined total T cell numbers and the distribution of Ag-specific and nonspecific T cells in different compartments following LM infection. Consistent with the reported data (4, 7), we found that LM infection resulted in depletion of total T cells not only in the spleen, but also in other compartments, including blood, liver, bone marrow, and lymph nodes (data not shown). In all organs examined, the P14 population expanded while the numbers of OT-I cells decreased following rLM-gp33 infection. Conversely, the OT-I population increased while the number of P14 cells declined in rLM-OVA-infected mice. Thus, depletion of nonspecific cells following LM infection occurs, although to varying degrees, in all compartments examined. Furthermore, we did not observe any increase in total or nonspecific T cells in the blood preceding their depletion, which otherwise would indicate increased trafficking of these cells to other organs, nor did we observe the return of nonspecific T cells by day 7 when the spleen was repopulated (data not shown). Nonspecific T cells do not become fully activated during LM infection (Figs. 2 and 5), and the increase in T cell number from days 3–7 is mostly by accumulation of activated (CD44high) T cells, which make up the majority (>80%) of the T cells by day 7 (Fig. 1). Together these results indicate that the repopulation of T cell compartments is mostly by the proliferation of Ag-specific T cells. Although it is difficult to completely rule out the possibility that some T cells may have trafficked to unusual places that we have not examined, our results together with previous studies by several groups indicate that depletion of nonspecific T cells is unlikely to be due to redistribution of these cells into other organs.
|
38% of P14 cells were TUNEL-positive in wtLM-infected mice, while <2% of P14 cells were TUNEL-positive in rLM-gp33-infected and PBS-treated mice. These results clearly demonstrate that P14 cells undergo apoptosis in wtLM-infected, but not in rLM-gp33-infected, mice. Thus, nonspecific T cells are depleted as a result of in situ death by apoptosis, while Ag-specific T cells are spared, providing conclusive evidence for selective depletion of nonspecific T cells during the early stage of LM infection.
|
Resting and activated lymphocytes differ in their sensitivities to various death signals and have dissimilar requirements for survival (20). We examined the activation phenotypes of nonspecific T cells before their depletion (Fig. 5). Within 24 h following LM infection, most T cells in the spleen up-regulated their surface expression of the early activation marker CD69 (Fig. 5A), and this included both Ag-specific and nonspecific T cells (Fig. 5B). Ag-specific T cells (P14 in rLM-gp33-infected mice and OT-I in rLM-OVA-infected mice) were further activated to divide and display a full spectrum of late activation phenotypes (CD44high, CD62Llow, and CD25high). On the other hand, nonspecific T cells (P14 cells in rLM-OVA-infected mice and OT-I in rLM-gp33-infected mice) did not divide or display any late activation markers. These results indicate that nonspecific T cells are activated in the early stage of LM infection, but only to a state of partial activation before their depletion. T cells receiving incomplete and inadequate activation signals do not progress through the cell cycle, but instead undergo apoptosis (20). Thus, it is possible that partial activation may lead to apoptosis of nonspecific T cells during the early stage of LM infection. Ag-specific T cells, on the other hand, are rescued from apoptosis by TCR engagement, which stimulates them to become fully activated, divide, and differentiate into effector cells to participate in the control of infection.
Depletion of nonspecific T cells during LCMV infection
IFN-
/IFN-
are strongly induced in many viral and bacterial infections (21, 22) and are known to stimulate naive T cells to a state of partial activation with up-regulation of CD69 surface expression (23, 24). Products of viral and bacterial pathogens, such as poly I:C, LPS, and undermethylated CpG DNA, induce IFN-/IFN--mediated partial activation of naive T cells (23, 24). Thus, we asked whether partial activation and selective depletion of nonspecific T cells also occur in the early stage of other infections. A previous study reported depletion of T cells during LCMV infection, but did not demonstrate whether the depletion is limited to nonspecific T cells (3). We cotransferred P14 and OT-I cells into recipient mice and examined these two populations on day 3 following LCMV infection (Fig. 6). LCMV infection resulted in depletion of OT-I and the host polyclonal CD8 T cell population, but not P14 cells (Fig. 6A). Most T cells, including both P14 and OT-I cells, expressed the early activation marker (CD69), while only P14 cells specific to the LCMV gp33 epitope displayed late activation markers (e.g., CD62Llow; Fig. 6B). Confocal microscopy showed that a substantial number of OT-I cells (40% with 200 cells counted), but few P14 cells (<2% with 200 cells counted), were TUNEL-positive in LCMV-infected mice (Fig. 6C). These results demonstrate that LCMV infection also induces partial activation of most T cells, which is followed by selective depletion of nonresponding T cells. Together, our results indicate that selective depletion of nonresponding T cells is probably a general phenomenon and an integral part of the T cell response to many infections.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
/IFN- are strongly induced, and IFN-/IFN- are known to activate naive T cells to up-regulate early activation markers without division (24, 25). Early activation of T cells by cytokines may produce a state of readiness that allows T cells to respond quickly upon encountering the cognate Ag. Indeed, IFN-/IFN- enhance the proliferation of naive T cells when they are stimulated by viable APC with Ag and appropriate costimulatory signals (24, 25). On the other hand, IFN-/IFN- have inhibitory effects when T cells do not receive appropriate stimulatory signals (24, 25). This is consistent with our finding that nonspecific T cells are induced to undergo apoptosis during the early stage of infection. Thus, early partial activation of T cells by cytokines may sensitize them to respond to Ags quickly or to die if they are not stimulated by appropriate antigenic and costimulatory signals.
Why are nonspecific T cells selectively depleted before the development of an effective Ag-specific response? At the beginning of any given infection, Ag-specific cells are very few, while nonspecific T cells are numerous in number and diverse in their TCR repertoire, some of which may become autoreactive as a result of their activation. Selective depletion of nonspecific T cells may serve to remove these activated T cells that are irrelevant in combating the infection. It is also possible that depletion of numerous nonspecific T cells may allow for maximal expansion of the Ag-specific T cell population by providing favorable space with more access to APC, cytokines, and growth factors. Indeed, depletion of nonspecific T cells is followed by massive proliferation of Ag specific T cells (1000-fold expansion) (26, 27, 28). Our results indicate that early activation and subsequent depletion of nonspecific T cells are integral elements of the immune response to proinflammatory infections and may serve an immunological function. Depletion of nonspecific T cells involves both naive and resting memory T cells (data not shown). Thus, attrition of bystander memory T cells may be part of a more global depletion of nonspecific T cells that occurs following certain heterologous infections.
What is the mechanism for selective depletion of nonspecific T cells? Activated T cells are prone to apoptosis, and their survival depends upon appropriate stimulation of TCR by antigenic peptides and costimulation (20). It is possible that death of nonspecific T cells is a default pathway subsequent to their partial activation by IFN-/IFN-. Signaling through the IFN-/IFN- receptor is required for initial T cell activation (24) and for depletion of T cells at the early stage of LCMV infection (3). A major pathway of intracellular signaling following IFN-/IFN- receptor engagement involves STAT1. However, our preliminary results show that T cells deficient in STAT1 are slightly more sensitive to apoptosis induced during the early stage of LM infection (unpublished observations). Recent studies have shown that IFN-/IFN- can inhibit and promote IFN- production by T cells by activating STAT1 and STAT4, respectively (21, 22, 29). Thus, IFN-/IFN- can signal through STAT4 in addition to STAT1, and it is possible that early T cell activation by IFN-/IFN- may involve the STAT4 signaling pathway. The survival and death of these activated T lymphocytes is probably further controlled by pro- and antiapoptotic factors. The expression of the antiapoptotic protein, Bcl-xL, is known to increase the resistance of T cells to Fas-induced apoptosis (30). However, Bcl-xL-transgenic T cells are equally sensitive to apoptosis induced during the early stage of LM infection (J. Jiang and H. Shen, unpublished observations). This result is consistent with previous findings that early T cell depletion during infection is independent of signaling through Fas and TNF receptors (7). We have preliminary results indicating that TNF-related apoptosis-inducing ligand (TRAIL) may be involved. We observed that T cell apoptosis during the early stage of LM infection is reduced in TRAIL knockout mice and by treatment with soluble death receptor 5 that blocks binding of TRAIL to its receptors (J. Jiang and H. Shen, unpublished observations). Elucidation of these underlying mechanisms may allow us to develop new avenues for modulation of the immune response.
In conclusion, our results uncover several important early events in the T cell response to infection and provide a foundation for understanding molecular and cellular factors involved in the initiation of effective T cell responses to infection.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Current address: Department of Microbiology and Immunology, Drexel University, College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129.
3 Current address: Office of Technology Transfer, Thomas Jefferson University, 1020 Locust Street, M60, Philadelphia, PA 19107.
4 Address correspondence and reprint requests to Dr. Hao Shen, Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104-6076. E-mail address: hshen{at}mail.med.upenn.edu
5 Abbreviations used in this paper: LM, Listeria monocytogenes; AICD, activation-induced cell death; LCMV, lymphocytic choriomeningitis virus; rLM, recombinant LM; wtLM, wild-type LM strain.
Received for publication October 24, 2002. Accepted for publication August 18, 2003.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
response to viral infection. Science 297:2063. and as immune regulators: a new look. Immunity 14:661.[Medline]
/-mediated inhibition and promotion of interferon gamma: STAT1 resolves a paradox. Nat. Immunol. 1:70.[Medline]
This article has been cited by other articles:
|
|
 |
|
  S. Baize, P. Marianneau, P. Loth, S. Reynard, A. Journeaux, M. Chevallier, N. Tordo, V. Deubel, and H. Contamin Early and Strong Immune Responses Are Associated with Control of Viral Replication and Recovery in Lassa Virus-Infected Cynomolgus Monkeys J. Virol., June 1, 2009; 83(11): 5890 - 5903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Bangs, D. Baban, H. J. Cattan, C. K.-F. Li, A. J. McMichael, and X.-N. Xu Human CD4+ Memory T Cells Are Preferential Targets for Bystander Activation and Apoptosis J. Immunol., February 15, 2009; 182(4): 1962 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Choi, H. Xu, Y. Geng, A. Colmone, H. Cho, and C.-R. Wang Bacterial infection alters the kinetics and function of iNKT cell responses J. Leukoc. Biol., December 1, 2008; 84(6): 1462 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Hamilton and S. C. Jameson The nature of the lymphopenic environment dictates protective function of homeostatic-memory CD8+ T cells PNAS, November 25, 2008; 105(47): 18484 - 18489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Zhang, Z. Zhang, B. Jin, S.-Y. Zhang, C.-B. Zhou, J.-L. Fu, and F.-S. Wang Cutting Edge: Programmed Death-1 Up-Regulation Is Involved in the Attrition of Cytomegalovirus-Specific CD8+ T Cells in Acute Self-Limited Hepatitis B Virus Infection J. Immunol., September 15, 2008; 181(6): 3741 - 3744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Carrero, H. Vivanco-Cid, and E. R. Unanue Granzymes Drive a Rapid Listeriolysin O-Induced T Cell Apoptosis J. Immunol., July 15, 2008; 181(2): 1365 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sakowicz-Burkiewicz, G. Nishanth, U. Helmuth, K. Drogemuller, D. H. Busch, O. Utermohlen, M. Naumann, M. Deckert, and D. Schluter Protein Kinase C-{theta} Critically Regulates the Proliferation and Survival of Pathogen-Specific T Cells in Murine Listeriosis J. Immunol., April 15, 2008; 180(8): 5601 - 5612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zwaferink, S. Stockinger, S. Reipert, and T. Decker Stimulation of Inducible Nitric Oxide Synthase Expression by Beta Interferon Increases Necrotic Death of Macrophages upon Listeria monocytogenes Infection Infect. Immun., April 1, 2008; 76(4): 1649 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Bradfute, K. L. Warfield, and S. Bavari Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection J. Immunol., March 15, 2008; 180(6): 4058 - 4066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fang, T. Miwa, H. Shen, and W.-C. Song Complement-Dependent Enhancement of CD8+ T Cell Immunity to Lymphocytic Choriomeningitis Virus Infection in Decay-Accelerating Factor-Deficient Mice J. Immunol., September 1, 2007; 179(5): 3178 - 3186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jablonska, K. E. Dittmar, T. Kleinke, J. Buer, and S. Weiss Essential Role of CCL2 in Clustering of Splenic ERTR-9+ Macrophages during Infection of BALB/c Mice by Listeria monocytogenes Infect. Immun., January 1, 2007; 75(1): 462 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Prlic, G. Hernandez-Hoyos, and M. J. Bevan Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response J. Exp. Med., September 4, 2006; 203(9): 2135 - 2143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jabbari, K. L. Legge, and J. T. Harty T cell conditioning explains early disappearance of the memory CD8 T cell response to infection. J. Immunol., September 1, 2006; 177(5): 3012 - 3018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alsharifi, M. Regner, R. Blanden, M. Lobigs, E. Lee, A. Koskinen, and A. Mullbacher Exhaustion of Type I Interferon Response following an Acute Viral Infection. J. Immunol., September 1, 2006; 177(5): 3235 - 3241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Overwijk, K. E. de Visser, F. H. Tirion, L. A. de Jong, T. W. H. Pols, Y. U. van der Velden, J. G. van den Boorn, A. M. Keller, W. A. Buurman, M. R. Theoret, et al. Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant J. Immunol., May 1, 2006; 176(9): 5213 - 5222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Carrero, B. Calderon, and E. R. Unanue Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes J. Exp. Med., April 17, 2006; 203(4): 933 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bahl, S.-K. Kim, C. Calcagno, D. Ghersi, R. Puzone, F. Celada, L. K. Selin, and R. M. Welsh IFN-Induced Attrition of CD8 T Cells in the Presence or Absence of Cognate Antigen during the Early Stages of Viral Infections J. Immunol., April 1, 2006; 176(7): 4284 - 4295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Foulds and H. Shen Clonal Competition Inhibits the Proliferation and Differentiation of Adoptively Transferred TCR Transgenic CD4 T Cells in Response to Infection. J. Immunol., March 1, 2006; 176(5): 3037 - 3043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Kim, J. J. Priatel, S.-J. Teh, and H.-S. Teh TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo J. Immunol., January 15, 2006; 176(2): 1026 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Tebo, M. J. Fuller, D. E. Gaddis, K. Kojima, K. Rehani, and A. J. Zajac Rapid Recruitment of Virus-Specific CD8 T Cells Restructures Immunodominance during Protective Secondary Responses J. Virol., October 15, 2005; 79(20): 12703 - 12713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Berg, E. Crossley, S. Murray, and J. Forman Relative Contributions of NK and CD8 T Cells to IFN-{gamma} Mediated Innate Immune Protection against Listeria monocytogenes J. Immunol., August 1, 2005; 175(3): 1751 - 1757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jiang, D. Gross, S. Nogusa, P. Elbaum, and D. M. Murasko Depletion of T Cells by Type I Interferon: Differences between Young and Aged Mice J. Immunol., August 1, 2005; 175(3): 1820 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Belz, K. Shortman, M. J. Bevan, and W. R. Heath CD8{alpha}+ Dendritic Cells Selectively Present MHC Class I-Restricted Noncytolytic Viral and Intracellular Bacterial Antigens In Vivo J. Immunol., July 1, 2005; 175(1): 196 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Feng, D. Zhang, D. Palliser, P. Zhu, S. Cai, A. Schlesinger, L. Maliszewski, and J. Lieberman Listeria-Infected Myeloid Dendritic Cells Produce IFN-{beta}, Priming T Cell Activation J. Immunol., July 1, 2005; 175(1): 421 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-K. Kim, M. Cornberg, X. Z. Wang, H. D. Chen, L. K. Selin, and R. M. Welsh Private specificities of CD8 T cell responses control patterns of heterologous immunity J. Exp. Med., February 22, 2005; 201(4): 523 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Zheng, J. Jiang, H. Shen, and Y. H. Chen Reduced Apoptosis and Ameliorated Listeriosis in TRAIL-Null Mice J. Immunol., November 1, 2004; 173(9): 5652 - 5658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dhanji, S.-J. Teh, D. Oble, J. J. Priatel, and H.-S. Teh Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors Blood, October 1, 2004; 104(7): 2116 - 2123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Auerbuch, D. G. Brockstedt, N. Meyer-Morse, M. O'Riordan, and D. A. Portnoy Mice Lacking the Type I Interferon Receptor Are Resistant to Listeria monocytogenes J. Exp. Med., August 16, 2004; 200(4): 527 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. O'Connell, S. K. Saha, S. A. Vaidya, K. W. Bruhn, G. A. Miranda, B. Zarnegar, A. K. Perry, B. O. Nguyen, T. F. Lane, T. Taniguchi, et al. Type I Interferon Production Enhances Susceptibility to Listeria monocytogenes Infection J. Exp. Med., August 16, 2004; 200(4): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Carrero, B. Calderon, and E. R. Unanue Listeriolysin O from Listeria monocytogenes Is a Lymphocyte Apoptogenic Molecule J. Immunol., April 15, 2004; 172(8): 4866 - 4874. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
