The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Longhi, M. P.
Right arrow Articles by Gallimore, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Longhi, M. P.
Right arrow Articles by Gallimore, A.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
The Journal of Immunology, 2005, 175: 7098-7102.
Copyright © 2005 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Murine CD59a Modulates Antiviral CD4+ T Cell Activity in a Complement-Independent Manner1

M. Paula Longhi2, Baalasubramanian Sivasankar, Nader Omidvar, B. Paul Morgan and Awen Gallimore

Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Wales, United Kingdom


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results and Discussion
 Disclosures
 References
 
CD59 blocks formation of the membrane attack complex of complement by inhibiting binding of C9 to the C5b-8 complex. To investigate a role for CD59 in promoting T cell responses, we compared T cell activation in CD59a-deficient (Cd59a–/–) and wild-type (WT) mice after in vitro stimulation and after infection with rVV. Virus-specific CD4+ T cell responses were significantly enhanced in Cd59a–/– mice compared with WT mice. Similarly, Cd59a–/– T cells responded more vigorously to in vitro stimulation with CD3-specific Abs compared with WT mice. This effect of CD59a on T cell proliferation was found to be complement-independent. Collectively, these results demonstrate that CD59a down-modulates CD4+ T cell activity in vitro and in vivo, thereby revealing another link between complement regulators and T cell activation.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results and Discussion
 Disclosures
 References
 
Human CD59 is a 18–20 kDa GPI-anchored protein expressed in all circulating cells and in most tissues (1). In common with other GPI-anchored proteins, it is found in membrane microdomains, lipid rafts, which serve as platforms for Ag receptor signaling complexes in lymphocytes. CD59 acts as a complement (C)3 regulator by inhibiting the formation of the membrane attack complex (2). Others have suggested that CD59 also acts as a costimulatory molecule for T cell activation. Ab-mediated cross-linking of CD59 on PMA-treated human T cells caused enhanced proliferation and IL-2 production (3).

To explore the role of CD59 in T cell activation in vivo, we examined T cell function in mice lacking the species analog, CD59a (4). T cell activity was compared in Cd59a–/– and Cd59a+/+ (wild-type; WT) mice after in vitro stimulation and after infection of mice with recombinant vaccinia virus (rVV). CD8+ T cell responses were unaltered in the absence of CD59a; however, CD4+ T cells displayed enhanced proliferation to several stimuli both in vivo and in vitro. C inhibition did not influence the enhanced responses, indicating that CD59a modulates CD4+ T cell activation independent of C.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results and Discussion
 Disclosures
 References
 
Mice

C57BL/6 (H-2b) mice (WT) were obtained from Harlan. B6.129-Cd59atm1Bpm (Cd59a–/–) mice were generated as described previously (4) and backcrossed onto the C57BL/6 background for eight generations. Cd59a–/– mice were intercrossed with the B6.129S4-C3tm1Crr (C3–/–) mice (5) also on the C57BL/6 background. Experiments were performed in compliance with Home Office regulations.

Cell culture

Yac-1 cells, T cells, and V8E, a mouse CD4+ T cell hybridoma (6) (provided by Dr. Annette Oxenius, University of Zurich, Zurich, Switzerland), were maintained in RPMI 1640 medium supplemented with 10% FCS, penicillin-streptomycin, L-glutamine, and 2-ME. V8E cells were transfected with CD59a using standard methods.

Infection with rVV and determination of antivirus response

rVV expressing the gp of lymphocytic choriomeningitis virus (LCMV) has been described previously (7). Mice received injections i.p. with 50 µl of rVVGP at 108 PFU/ml. At day 3 and 8 after infection, ovaries were harvested for virus titers, and immunostaining and spleens were harvested for CTL assays and T cell proliferation assays. For memory responses, spleens were harvested 6 wk after infection, and CTL assays and CD4+ T cell proliferation assays were performed.

Fluorescence staining

Cy5-conjugated Abs were used for CD4 staining (Caltag Laboratories). Cells were incubated with 5 µg/ml mAb for 30 min, washed, and resuspended in FACS buffer. IFN-{gamma} staining was performed using IFN-{gamma}-FITC mAbs (BD Pharmingen) after incubating ovary-derived lymphocytes for 4 h at 37°C in the presence of ionomycin (1 µg/ml), PMA (20 ng/ml), and monensin (3 µM) (Sigma-Aldrich). CFSE staining (Molecular Probes) was conducted by incubating the cells for 10 min at 37°C with 0.5 µM CFSE. In all cases, cells were resuspended in FACS buffer and analyzed by FACS (FACSCalibur; BD Biosciences).

Immunoprecipitation and Western blotting

Immunoprecipitation was performed as described previously (8). Lysates of mouse CD4+ or CD8+ T cells were incubated with 10 µg of mouse mAb against CD59a (mCD59.4) (9) and 50 µl of protein A-Sepharose beads for 2 h at 4°C. The immunoprecipitates were washed in lysis buffer and boiled in nonreducing SDS-PAGE sample buffer. Beads were removed by centrifugation, and supernatants were resolved on nonreducing 12% SDS-PAGE and transferred to nitrocellulose. The membrane was probed with the CD59a-specific mAb mCD59.1 as described previously (9).

T cell proliferation

CD4+ and CD8+ T cells from single-cell suspensions of splenocytes were purified by positive MACS MicroBeads selection (Miltenyi Biotec). To produce APCs, spleen cells were panT depleted (Dynabeads; Dynal Biotech) and irradiated with 2400 cGy CD4+, or CD8+ cells (2 x 104 cells) were incubated with 105 APCs and 1 µg/ml anti-CD3 mAb in a 96-multiwell (MW) plate. Cell proliferation was assessed by thymidine incorporation or CFSE FACS analysis at day 3. For anti-CD28 and anti-CD3 mAb stimulation, 105 CD4+ T cells were incubated in a 96-MW plate with 2 µg/ml anti-CD28 and 2 µg/ml anti-CD3 (Leinco Technologies). Vaccinia-specific CD4+ T cell proliferation was performed by incubation of 105 CD4+ T cells with 6 x 105-irradiated splenocytes and 2.5 µg/ml P13 peptide (GLNGPDIYKGVYQFKSVEFD) (LCMV-GP, I-Ab) or P61 peptide (SGEGWPYIACRTSVVGRAWE) (LCMV-NP, I-Ab). CD8+ T cell proliferation was conducted against the Db-restricted peptide gp33. Cells were incubated for 6 days, and thymidine was added for the last 18 h.

Exogenous incorporation of CD59a

CD59a was purified as described previously (10). CD4+ T cells (5 x 106 cells) were incubated with 5 µg of CD59a for 20 min at 37°C to permit incorporation via the GPI anchor. Cells were then washed and incubated for another 2 h to allow migration of CD59a into lipid rafts (11).

CTL assay

Spleen cells (4 x 106 cells) were stimulated in vitro with 1 x 106 gp33 (KAVYNFATM) (LCMV-GP, Db) peptide-loaded (10–5 M) splenocytes, and IL-2 was added at day 2. After 1 wk, cells were restimulated with 1 x 106 gp33 splenocytes and IL-2 (10 U/ml). rVV-specific CTL activity was measured 5 days later as described previously (12).

Virus titers

rVVGP titers were determined in ovaries at day 3 and 8 postinfection. Ovaries were homogenized and incubated on a monolayer of TK– cells as described previously (13).

CD59a cross-linking and IL-2 ELISA

V8E, a mouse CD4+ T cell hybridoma negative for CD59a expression by FACS, was transfected with CD59a as described (9). Purified CD4+ T cells from Cd59a–/– or WT mice or V8E cells, untransfected or transfected with CD59a, were incubated with mCD59.1 or isotype-control mAb for 15 min at 4°C. After washing, cells were plated at 105 cells/well in triplicate in a 96-MW plate. Where appropriate, 5 µg/ml F(ab')2 rabbit anti-rat IgG Ab (Serotec) was added to the wells to cross-link (3). Cells were activated with 0.5 ng/ml PMA and incubated at 37°C. After 18 h, IL-2 was measured by ELISA according to the manufacturer’s instructions (BD Pharmingen).

C inhibition

For inhibition of C activity in vitro, 1 µg/ml recombinant human soluble CR1 (sCR1; gift from T Cell Sciences) was added to each well of a 96-MW plate. Cell proliferation was assayed after 3 days by thymidine incorporation. For in vivo inhibition, mice received injections i.v. daily with 20 mg/kg sCR1. To confirm C inhibition, mice were bled daily, and serum was tested for C hemolytic activity using rabbit erythrocytes (RbE) sensitized with mouse anti-RbE antiserum. Serial dilutions of test or control sera were incubated with 2% RbE. Hemolysis was measured by absorbance in supernatants at 415 nm ([A415 (sample) – A415 (min)]/[A415 (max) – A415 (min)] x100). Hemolytic activity in samples taken 24 h posttreatment was always <15% of controls.


   Results and Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
Disclosures
 References
 
Induction of IL-2 production by anti-CD59 mAb

Previous cross-linking experiments indicate that human CD59 acts as an accessory molecule for T cell activation (3). To confirm this finding in the mouse system, we stimulated purified splenic CD4+ T cells with PMA, CD59a-specific mAb and cross-linking anti-Ig. CD59a cross-linking on mouse CD4+ T cells did not induce IL-2 production (Fig. 1A). Because this may be due to the low level of CD59a on mouse lymphocytes (as assessed by FACS; Ref.9), we overexpressed CD59a in a murine CD4+ T cell hybridoma (V8E) (6). Transfected cells expressed CD59a (Fig. 1C), and, when stimulated with PMA, cross-linking of CD59a yielded enhanced IL-2 production in comparison to untransfected cells subjected to the same stimuli (Fig. 1B). These data indicate that when CD59a is expressed at a sufficient level on murine T cells, cross-linking CD59a does enhance IL-2 production in a manner similar to that described for human T cells.



View larger version (16K):
[in this window]
[in a new window]
  		FIGURE 1. CD59a cross-linking induces secretion of IL-2. Expression of CD59a in VE8 and VE8-CD59a cells was detected by flow cytometry (C). Purified CD4+ splenic T cells from WT and Cd59a–/– mice (A) or VE8 and VE8-CD59a cells (B) were incubated with mCD59.1 mAb followed by an anti-Ig Ab. After 18 h, IL-2 production was detected by ELISA. Values shown are mean ± SD. The results are representative of two experiments. Statistical significance (*) was evaluated using the Student’s t test (p < 0.001).

 
Mouse T cells express CD59a

CD59a expression is not detectable on murine lymphocytes by FACS (9). More sensitive methods were therefore used to determine whether primary murine CD4+ and CD8+ T cells express CD59a. CD59a expression was detectable by RT-PCR (data not shown) and immunoprecipitation, followed by Western blotting (Fig. 2A) in both CD4+ and CD8+ T cells from WT but not Cd59a–/– mice.



View larger version (30K):
[in this window]
[in a new window]
  		FIGURE 2. rVVGP-specific CD8+ T cell activity and CD4+ T cell proliferation. CD59a expression was analyzed from immunoprecipitates of purified CD4+ T and CD8+ T cells from WT and control T cells from Cd59a–/– mice. Expression was detected using specific Abs in Western blotting (A). CD8+ T cell cytotoxic activity (B) and cell CD8+ T cell proliferation (C) was analyzed at day 8 after rVVGP infection. Nonspecific lysis in the experiment shown in (B) was <10%. CD4+ T cells purified from rVVGP-infected mice were tested for proliferation against peptides p61 and p13 8 days (D) and 6 wk (E) postinfection. Mice were analyzed individually, and values shown are the mean ± SEM (n = 3 mice/group). The results are representative of three independent experiments. Statistical significance was evaluated using the Student’s t test.

 
Immune responses in Cd59a–/– mice following infection with rVV

To determine whether physiological levels of CD59a plays any role in modulation of murine T cell activation in vivo, T cell responses were compared in WT and Cd59a–/– mice after rVVGP infection. rVVGP contains several MHC-restricted peptide epitopes recognized by T cells in WT mice. One peptide, gp33, derived from the gp, is presented by H2-Db to CD8+ T cells (14), whereas another epitope, p13, is presented by H2-I-Ab to CD4+ T cells (12). No significant difference in CTL activity (Fig. 2B) or Ag-specific CD8+ T cell proliferation (Fig. 2C) was observed between groups of mice at 8 days after infection. There was also no significant difference in CTL activity measured at day 42 after infection (data not shown). Virus-specific CD4+ T cell proliferation assays performed at the same time points revealed stronger proliferative responses to the specific peptide, p13, in Cd59a–/– mice compared with WT mice, whereas no differences were observed in background proliferation to an irrelevant peptide, p61 (Figs. 2, D and E). These data are similar to those reported recently using CD55-deficient mice, where CD4+ T lymphocytes from these mice were found to proliferate more vigorously in response to a range of Ags compared with WT mice (15, 16). Another study reported that T cells isolated from Ly-6A-deficient animals also proliferate more vigorously than those isolated from their WT counterparts (17). Interestingly, Ly-6A, CD59, and CD55 are all GPI-anchored molecules localized in lipid rafts, and all have previously been found in cross-linking studies to promote T cell activation in vitro (3, 17, 18). Despite this, all three molecules negatively regulate T cell activity in vivo. Because GPI-linked proteins weakly associate with protein tyrosine kinases, it is possible that they can act either as positive or negative regulators of T cell activation by sequestering signaling molecules or interfering with assembly of signaling complexes in lipid rafts, the net effect dependent upon the trigger.

Immune responses in ovaries and virus titers

To determine whether the enhanced proliferation of gp-specific CD4+ T cells observed after in vitro stimulation reflected a stronger anti-viral CD4+ T cell response in vivo, numbers of CD4+ T cells at the site of rVVGP infection (ovary) were compared in WT and Cd59a–/– mice at day 8 after infection. Higher numbers of infiltrating CD4+ T cells (Fig. 3A) and IFN-{gamma}-producing CD4+ T cells (Fig. 3B) were observed in the ovaries of Cd59a–/– mice compared with WT mice. The same analysis was performed for ovary-infiltrating CD8+ T cells (Figs. 3, C and D). Although higher numbers of CD8+ T cells were observed in the ovaries of Cd59a–/– mice compared with WT mice, this difference was not statistically significant and may reflect enhanced helper CD4+ T cell activity rather than a direct effect of CD59a on CD8+ T activity. Virus titers were also compared in both groups of mice at days 3 and 8 postinfection. Virus titers were significantly lower in Cd59a–/– mice compared with WT mice at day 3 postinfection, whereas both groups of mice had controlled the infection by day 8 (Fig. 3E). These data indicate that the more robust CD4+ T cell response observed in Cd59a–/– mice does not reflect an inability to clear the virus efficiently but may rather contribute to more rapid control of the infection.



View larger version (23K):
[in this window]
[in a new window]
  		FIGURE 3. rVVGP clearance in Cd59a–/– mice. Ovary-infiltrating lymphocytes were stained for intracellular IFN-{gamma}, CD4, and CD8 expression at day 8 postinfection and analyzed by FACS. Total numbers of infiltrating CD4+ and CD8+ T cells are shown in A and C, respectively, and total numbers of IFN-{gamma} producing CD4+ and CD8+ T cells are shown in B and D, respectively. Virus titers in the ovaries of infected mice were determined at day 3 and 8 postinfection (E). Each symbol represents an individual mouse, and similar data were observed in two independent experiments. Mean titers are also indicated in each graph. Statistical significance was evaluated using the Student’s t test.

 
Analysis of CD4+ T cell proliferation in vitro

We next compared proliferation of T cells from WT mice and Cd59a–/– mice after in vitro stimulation with CD3-specific mAb and APCs. Although no difference was observed in proliferation of CD8+ T cells (Fig. 4B), CD4+ T cells from Cd59a–/– mice exhibited more proliferation in vitro compared with T cells from WT mice (2.5-fold increase; Fig. 4A). The increase in proliferation of CD4+ T cells from Cd59a–/– mice compared with WT mice was only apparent when CD3-specific mAb and APCs were used for in vitro stimulation and not when CD3- and CD28-specific Abs were used (compare Figs. 4, B and C). To determine whether CD59a expression on APCs affected proliferation of the responding T cells, CD4+ T cells were incubated with APCs from WT or Cd59a–/– mice. CD4+ T cell proliferation was not influenced by the presence or absence of CD59a on APCs, indicating that the difference in proliferation of CD4+ T cells from WT and Cd59a–/– mice is due to expression of CD59a on the T cells (data shown). Incorporation of GPI-anchored CD59a into CD4+ T cells from Cd59a–/– mice (Fig. 4D) caused a reduction in proliferation to levels the same as cells from WT mice (Fig. 4E). Together, these data imply that CD59a down-modulates CD4+ T cell proliferation and requires the presence of APCs to exert this effect. It is possible that CD59a engages with a ligand on the APC or, alternatively, a soluble factor produced by the APC. To test the possibility that C activation and formation of the membrane attack complex mediates CD59a modulation of T cell activity, CD4+ T cells purified from both WT and Cd59a–/– mice were stimulated with CD3-specific mAb and APCs in the presence and absence of a soluble inhibitor of C (sCR1). sCR1 blocks activation of the classical and alternative pathways of C by binding C3b and C4b and mediating proteolytic degradation of these molecules (19). Inhibition of C in vitro did not affect the proliferative response of Cd59a–/– T cells, indicating that the enhanced proliferation was C independent (Fig. 5A). To determine whether this was also true in vivo, mice infected with rVVGP received injections daily with sCR1, a treatment that efficiently inhibited C throughout the course of the experiment. gp-specific CD4+ T cell responses were measured 9 days after infection, and no difference was observed in virus-specific proliferative responses induced in the presence or absence of C inhibition (Fig. 5B). To confirm this result, Cd59a–/– mice were intercrossed with C3–/– mice and then infected with rVVGP. Virus-specific CD4+ T cell responses were enhanced equally in Cd59a–/– and Cd59a–/–C3–/– mice compared with WT and C3–/– mice (Fig. 5C). These data demonstrate that the enhanced proliferation of Cd59a–/– CD4+ T cells is C independent and contrast with a recent report for the C regulator CD55 (15). Enhanced CD4+ proliferative responses observed in CD55-deficient mice were largely, although not exclusively, C dependent.



View larger version (37K):
[in this window]
[in a new window]
  		FIGURE 4. In vitro proliferation assays. Purified CD4+ or CD8+ T cells (>90%) were CFSE labeled and incubated with anti-CD3 mAb and APCs (A and B) or anti-CD28 mAb (C). Calculation of the number of mitotic events was performed as described previously (22 ). One representative result of at least three independent experiments is shown. Values indicating mitotic events are the means of three experiments ± SD. To confirm that lack of CD59a expression was responsible for enhanced proliferation of T cells from Cd59a–/– mice, lymphocytes were incubated with GPI-anchored CD59a (CD59a-GPI) before the proliferation assay (E). Incorporation of CD59a-GPI on CD4+ T cells was confirmed by immunostaining (D). Values shown represent the mean ± SD. The experiment was performed on three separate occasions. Statistical analysis was performed by the Student’s t test.

 


View larger version (23K):
[in this window]
[in a new window]
  		FIGURE 5. Role of C in CD4+ T cell proliferation. C was inhibited in vitro in assays where CD4+ T cells were stimulated with CD3-specific mAb and APCs (A). Data are representative of two experiments, and values are shown as mean ± SD. C was inhibited in vivo by administration of sCR1 to mice for the first 9 days of infection with rVVGP (B). In vivo experiments were repeated with Cd59a–/–C3–/– mice (C). Mice were individually analyzed, and the values shown indicate the mean ± SEM (n = 3 mice/group). The results were analyzed statistically by the Student’s t test.

 
In summary, this report identifies a role for the GPI-anchored C regulator CD59a in negative modulation of T cell activity in vivo. Due to the GPI anchor, CD59a is sequestered in membrane microdomains, which serve as platforms for Ag receptor signaling complexes in lymphocytes. CD59a may influence the rearrangement of lipid rafts after APC/CD4+ T cell association. T cell activation induces a rapid compartmentalization of signaling machinery into lipid rafts. Costimulatory molecules are important for this redistribution (20), and it is possible that the presence of CD59a within rafts result in recruitment of different raft-associated kinases leading to modulation of T cell activity. No difference was found with CD8+cells, possibly due to differences in lipid raft composition between CD4+ and CD8+ cells (21).

Further analyses of Cd59a–/– mice are required to provide insight into the precise nature of the molecular events underlying the effect of CD59a on T cell activity. Such an understanding will reveal pathways through which CD59a and its human analog may be exploited for therapeutic approaches designed to either up-regulate beneficial T cell responses or down-modulate those that are harmful.


   Acknowledgments
 
We thank Drs. Claire Harris and Paul Brennan for critical reading of the manuscript and Dr. Rossen M. Donev for advice.


   Disclosures
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 Disclosures
References
 
The authors have no financial conflict of interest.


   Footnotes
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 M.P.L. is supported by a Prize Studentship awarded by The Wellcome Trust (ref. no. 073055). B.P.M. and N.O. are supported by a Wellcome Trust program grant (ref. no. 068590). B.S. is supported by the Wellcome Trust International Travelling Research Fellowship (ref. no. 068280). A.G. is supported by a Medical Research Council Senior Fellowship (ref. no. G117/488). Back

2 Address correspondence and reprint requests to Dr. M. Paula Longhi, Medical Biochemistry and Immunology, School of Medicine, Cardiff University, CF14 4XN Wales, U.K. E-mail address: longhimp{at}Cardiff.ac.uk Back

3 Abbreviations used in this paper: C, complement; WT, wild type; rVV, recombinant vaccinia virus; LCMV, lymphocytic choriomeningitis virus; MW, multiwell; sCR1, recombinant human soluble CR1; RbE, rabbit erythrocyte. Back

Received for publication June 9, 2005. Accepted for publication September 20, 2005.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 Disclosures
 References
 

  1. Meri, S. W. H., P. J. Lachmann. 1991. Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues. Lab. Invest. 65: 532-537. [Medline]
  2. Farkas, I., L. Baranyi, Y. Ishikawa, N. Okada, C. Bohata, D. Budai, A. Fukuda, M. Imai, H. Okada. 2002. CD59 blocks not only the insertion of C9 into MAC but inhibits ion channel formation by homologous C5b-8 as well as C5b-9. J. Physiol. 539: 537-545. [Abstract/Free Full Text]
  3. Korty, P., C. Brando, E. Shevach. 1991. CD59 functions as a signal-transducing molecule for human T cell activation. J. Immunol. 146: 4092-4098. [Abstract]
  4. Holt, D. S., M. Botto, A. E. Bygrave, S. M. Hanna, M. J. Walport, B. P. Morgan. 2001. Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria. Blood 98: 442-449. [Abstract/Free Full Text]
  5. Wessels, M., P. Butko, M. Ma, H. Warren, A. Lage, M. Carroll. 1995. Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity. Proc. Natl. Acad. Sci. USA 92: 11490-11494. [Abstract/Free Full Text]
  6. Oxenius, M. B., D. Mathis, C. Benoist, R. M. Zinkernagel, H. Hengartner. 1997. Functional in vivo MHC class II loading by endogenously synthesized glycoprotein during viral infection. J. Immunol. 158: 5717-5726. [Abstract]
  7. Bachmann, M. F., T. M. Kundig, G. Freer, Y. Li, C. Y. Kang, D. H. Bishop, H. Hengartner, R. M. Zinkernagel. 1994. Induction of protective cytotoxic T cells with viral proteins. Eur. J. Immunol. 24: 2228-2236. [Medline]
  8. Baalasubramanian, S., C. L. Harris, R. M. Donev, M. Mizuno, N. Omidvar, W.-C. Song, B. P. Morgan. 2004. CD59a is the primary regulator of membrane attack complex assembly in the mouse. J. Immunol. 173: 3684-3692. [Abstract/Free Full Text]
  9. Harris, C. L., S. M. Hanna, M. Mizuno, D. S. Holt, K. J. Marchbank, B. P. Morgan. 2003. Characterization of the mouse analogues of CD59 using novel monoclonal antibodies: tissue distribution and functional comparison. Immunology 109: 117-126. [Medline]
  10. Stefanova, I., V. Horejsi. 1991. Association of the CD59 and CD55 cell surface glycoproteins with other membrane molecules. J. Immunol. 147: 1587-1592. [Abstract]
  11. van den Berg, C., T. Cinek, M. Hallett, V. Horejsi, B. Morgan. 1995. Exogenous glycosyl phosphatidylinositol-anchored CD59 associates with kinases in membrane clusters on U937 cells and becomes Ca2+-signaling competent. J. Cell Biol. 131: 669-677. [Abstract/Free Full Text]
  12. Oxenius, A., U. Karrer, R. M. Zinkernagel, H. Hengartner. 1999. IL-12 is not required for induction of type 1 cytokine responses in viral infections. J. Immunol. 162: 965-973. [Abstract/Free Full Text]
  13. Fitzgerald, J. C., G.-P. Gao, A. Reyes-Sandoval, G. N. Pavlakis, Z. Q. Xiang, A. P. Wlazlo, W. Giles-Davis, J. M. Wilson, H. C. J. Ertl. 2003. A simian replication-defective adenoviral recombinant vaccine to HIV-1 Gag. J. Immunol. 170: 1416-1422. [Abstract/Free Full Text]
  14. Whitton, J. L., J. R. Gebhard, H. Lewicki, A. Tishon, M. B. Oldstone. 1988. Molecular definition of a major cytotoxic T-lymphocyte epitope in the glycoprotein of lymphocytic choriomeningitis virus. J. Virol. 62: 687-695. [Abstract/Free Full Text]
  15. Liu, J., T. Miwa, B. Hilliard, Y. Chen, J. D. Lambris, A. D. Wells, W.-C. Song. 2005. The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J. Exp. Med. 201: 567-577. [Abstract/Free Full Text]
  16. Heeger, P. S., P. N. Lalli, F. Lin, A. Valujskikh, J. Liu, N. Muqim, Y. Xu, M. E. Medof. 2005. Decay-accelerating factor modulates induction of T cell immunity. J. Exp. Med. 201: 1523-1530. [Abstract/Free Full Text]
  17. Stanford, W. L., S. Haque, R. Alexander, X. Liu, A. M. Latour, H. R. Snodgrass, B. H. Koller, P. M. Flood. 1997. Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice. J. Exp. Med. 186: 705-717. [Abstract/Free Full Text]
  18. Davis, L., S. Patel, J. Atkinson, P. Lipsky. 1988. Decay-accelerating factor functions as a signal transducing molecule for human T cells. J. Immunol. 141: 2246-2252. [Abstract]
  19. Kalli, K., D. Fearon. 1994. Binding of C3b and C4b by the CR1-like site in murine CR1. J. Immunol. 152: 2899-2903. [Abstract]
  20. Martin, M., H. Schneider, A. Azouz, C. E. Rudd. 2001. Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function. J. Exp. Med. 194: 1675-1682. [Abstract/Free Full Text]
  21. de Mello Coelho, V., D. Nguyen, B. Giri, A. Bunbury, E. Schaffer, D. Taub. 2004. Quantitative differences in lipid raft components between murine CD4+ and CD8+ T cells. BMC Immunology 5: 2
  22. Yamazaki, S., T. Iyoda, K. Tarbell, K. Olson, K. Velinzon, K. Inaba, R. M. Steinman. 2003. Direct expansion of functional CD25+CD4+ regulatory T cells by antigen-processing dendritic cells. J. Exp. Med. 198: 235-247. [Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Immunol.Home page
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]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Longhi, M. P.
Right arrow Articles by Gallimore, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Longhi, M. P.
Right arrow Articles by Gallimore, A.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS