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* Institute of Integrative Biology, Molecular Biomedicine, Swiss Federal Institute of Technology, Zürich-Schlieren, Switzerland;
Laboratory for Immunological Research, Schering-Plough, Dardilly, France; and
Institut National de la Santé et de la Recherche Medicale, University of Nice-Sophia Antipolis, Valbonne, France
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Abstract |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionDisclosuresReferences |
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Dendritic cells (DC)3 are key instigators of both Th1 and Th2 immune responses. Several types of DC have been identified including myeloid, lymphoid, and plasmacytoid DC (pDC), which have been shown to differently promote Th1 or Th2 responses according to their origin and their maturation (5, 6). Skin DC are considered to play an important role in priming T cell immune responses against L. major. Indeed, mouse Langerhans cells (LC), a well-characterized DC subset residing in the epidermis, have been shown to internalize L. major parasites and migrate to skin draining lymph nodes, where they can activate specific CD4+ T cells (7). However, a critical role of LC for the induction of protective Th1 responses has been questioned recently, as C57BL/6 mice lacking MHC class II (MHCII) expression exclusively on LC display a healing phenotype, upon inoculation of high numbers of parasites (8). Furthermore, DC harboring parasites in draining lymph nodes 3 days after infection were found negative for langerin mRNA, a LC-specific marker (9, 10), thus suggesting that they do not belong to the LC population. Although these data do not exclude a role of LC, they suggest that other DC subsets might be the key players in initial transport and presentation of L. major. In particular, the role of dermal DC (DDC), another population of skin DC, has not been thoroughly investigated, possibly due to the lack of markers allowing discrimination of DDC and lymph node resident DC. Indeed, a subset of lymph node resident DC has been recently shown to acquire skin-derived soluble Ags, which are drained through the lymph into the conduit network and to contribute to activation of specific T cells (11, 12). Whether conduit-associated DC may also play a role during L. major infection remains to be investigated.
By taking advantage of a panel of tissue- and cell-specific markers, we here show that in the L. major mouse model the initiation of specific immune responses is mediated by a population of CD11chighCD11bhighCD8–langerin– DC, which reside in lymph nodes and acquire soluble Ags transported through the lymph. Prevention of skin DC migration through early removal of the infection site did not affect L. major-Ag presentation by resident DC and did not preclude activation of L. major-specific naive CD4+ T cells, thus indicating that skin-derived DC migration is not required for initiation of L. major-specific T cell responses.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionDisclosuresReferences |
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BALB/c, C57BL/6 (from Charles River Laboratories), B10.D2 (from Harlan Breeders), WT15 (encoding a LACK-specific TCR (13)), and DO11.10 mice (encoding a TCR specific for OVA323–339) were bred and maintained in our animal colony (BioSupport) free of specific pathogens. Mice used for experiments were 8–12 wk old. The animal ethics committee approved experiments. L. major parasites were propagated in vivo and, after recovery, grown in Schneider Drosophila Medium supplemented with L-glutamine, penicillin/streptomycin, and 20% FCS for 8–10 days in vitro before usage for infection. Typically, 2 x 106 stationary phase promastigotes (WHOM/IR/–/173) were injected s.c. in footpads or intradermally (i.d.) in the ears. The main results shown were verified with MHOM/IL/80/Friedlin (provided by P. Scott, University of Pennsylvania, Philadelphia, PA) and MHOM/IL/81/FE/BNI (provided by C. Bogdan, University of Freiburg, Freiburg, Germany). In experiments involving removal of the infection site, parasites were injected in a volume of 2 µl in the tip of the ears using a Hamilton syringe fitted with a 30.5-gauge needle. Five hours later, the infection site was surgically removed, as described (11). In some experiments, L. major parasites and OVA (grade V; Sigma-Aldrich) (200 µg in 2 µl) were injected in the same ear at two adjacent sites.
Isolation and purification of populations of lymph node cells
Draining lymph nodes from infected mice were isolated at different times after infection and digested in medium containing 1 mg/ml collagenase-D (Worthington Biochemical) at 37°C for 1 h. Lymph node cells were stained and analyzed by flow cytometry as described below. CD11c+ cells were positively selected by sorting with magnetic beads conjugated with anti-CD11c Ab (Miltenyi Biotec). The negative fraction was further positively selected with anti-MHCII Ab-conjugated beads. For isolation of different subsets, purified CD11c+ cells were stained as indicated below and purified by cell sorting (purity 
95%) using BD FACS Vantage.
FACS analysis of DC subsets
For surface molecules analysis, lymph node cells were stained with allophycocyanin-labeled anti-CD11c and PerCP-labeled anti-CD11b Abs, in combination with anti-Gr-1, anti-I-Ad, anti-CD8, anti-CD205 (NLDC-145) FITC-labeled Abs, or with the purified anti-gp40 followed by biotin-labeled-anti rat IgG2a and FITC-labeled streptavidin (all Abs obtained from BD Pharmingen, except anti-CD205 which came from Serotec). PE-labeled anti-PDCA-1 Ab was from Miltenyi Biotec. For langerin staining, cells were fixed with 1% paraformaldehyde in PBS, then permeabilized with 0.1% saponin in PBS and stained with purified anti-langerin (929F3) Ab (14) followed by biotin-labeled anti-rat IgG and PerCP-streptavidin. After extensive washing in PBS, surface staining of CD11c and CD11b molecules was performed.
T cell activation in vitro
Titrated numbers of CD11c+, CD11c-, or FACS-sorted cell subsets were cultured with 2–5 x 104 LMR7.5 hybridoma cells (15) or with 105 WT15-transgenic naive CD4+ T cells, purified by beads sorting, in IMDM supplemented with 7% heat-inactivated FCS, 2-ME (50 µM), penicillin (100 µg/ml), and streptomycin (100 U/ml) in U-bottom 96- well plates. Specific T cells responses were assessed by measuring IL-2 production in 24–48 h culture supernatants by ELISA or [3H]thymidine incorporation after 48 h. In some experiments, titrated numbers of FACS-sorted DC were cultured with 5 x 104 CFSE-labeled (Molecular Probes, 2.5 µM) WT15 or DO11.10 purified CD4+ T cells. After 3 days, T cells were stained with PE-labeled anti-CD4 and allophycocyanin-labeled anti-CD25 Abs (both from BD Pharmingen) and analyzed by flow cytometry.
Skin painting
Skin painting was performed by painting the dorsal site of the ears with 5-chloromethylfluorescein (CMFDA) (Molecular Probes) dissolved in a 50/50 (v/v) acetone-dibutyl phtalate (DBP) mixture (final concentration 0.5 mM, 50 µl/ear). When skin painting was combined with L. major infection, parasites were injected in the ears (in a 2 µl volume), and the skin overlaying the infection site was painted immediately after infection with CMFDA dissolved in acetone. Cells from draining lymph nodes were collected 24 h later and analyzed by flow cytometry.
T cell activation in vivo
Splenocytes of naive transgenic WT15 CD4+ T cells were enriched for CD4+ T cells by negative selection removing CD8+, MHCII+, and CD11b+ cells with specific Abs coupled to magnetic beads (Miltenyi Biotec). Purified CD4+ T cells were labeled with 5 µM CFSE (Molecular Probes) and injected i.v. into naive BALB/c mice. Mice were infected with L. major parasites in the ears 24 h later or left untreated. In some mice, the infection site was removed 5 h after infection. Five days after infection, cells from draining lymph nodes were collected, stained with PE-labeled anti-CD4, biotin-labeled anti-CD62L, or anti-CD44 Abs followed by allophycocyanin-labeled streptavidin (all from BD Pharmingen).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionDisclosuresReferences |
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We first studied the kinetics of L. major Ag presentation in draining lymph nodes following infection. Susceptible BALB/c and resistant B10.D2 mice were infected and CD11c+ and CD11c– cells were isolated from draining lymph nodes at indicated days to assess their capacity to present L. major Ag by measurement of IL-2 production upon coculture with the LACK-specific T cell hybridoma LMR7.5 or naive transgenic WT15 cells.
In both resistant and susceptible mice, CD11c+ but not CD11c– cells, activated the T cells to produce IL-2 as early as 24 h after infection. Ag presentation rapidly declined and became negligible by day 7 postinfection (Fig. 1, a and b). Notably, a second wave of presentation started between days 15 and 21 after infection in both BALB/c (Fig. 1b) and B10.D2 mice (data not shown). However, inoculates below 104 parasites did not result in Ag presentation when assessed at day 28 after infection (Fig. 1b, data not shown) suggesting that the second wave recommences >day 28, or that parasite growth is effectively controlled early after infection with very low numbers (i.e., 103). Importantly, similar results were observed comparing s.c. (footpad) and i.d. (ear) infection.
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Distinct subsets of CD11c+ cells are detected in draining lymph nodes in early phases of L. major infection
Previous work has suggested that L. major-presenting cells belong to the CD11c+CD11b+ fraction of lymph node cells (16, 17, 18). However whether these cells represent one single population or consist of different subsets, possibly deriving from different tissues, remains unclear. To better characterize these cells, we used a panel of Abs specific for different cell surface markers including Gr-1, I-Ad, CD8 and the recently described LC-specific marker langerin (9, 10). We distinguished five different subsets according to expression levels of CD11c and CD11b in draining lymph nodes of BALB/c mice. These included 1) CD11clowCD11bhigh cells (subset I); 2) CD11chighCD11bhigh cells (subset II); 3) CD11clowCD11blow cells (subset III); 3) CD11chighCD11blow cells (subset IV); and 5) CD11clowCD11bnegative cells (subset V) (Fig. 2a).
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3% of all CD11c+ cells) and absolute numbers and showed poor expression of Gr-1 and MHCII. However, upon infection this subset increased substantially (6.3-fold) and cells expressed high levels of Gr-1 and intermediate MHCII (Fig. 2, b and c). Cells in subset I were CD8– and langerin– (Fig. 2c). These data suggest that CD11clowCD11bhighGr-1+ cells are recruited to lymph nodes rapidly after infection and that this population does not contain any LC.
On the contrary, frequencies and absolute numbers of cells in subsets II, III, and IV were only modestly increased upon infection (Fig. 2b). Subset II (CD11chighCD11bhigh cells) was negative for langerin and contained a fraction of cells expressing CD8 (20% of cells) in both naive and infected mice. A subpopulation of subset II also expressed Gr-1 (53%) after infection, possibly representing freshly recruited cells. Subset II showed highest expression of MHC class II and the costimulatory molecules CD40 and CD86 (Table I), suggesting they are more mature than the other subsets. Subsets III and IV expressed negligible levels of Gr-1 and contained a significant fraction of langerin+ cells (15 and 35% of gated cells, respectively). Moreover, cells in subset IV contained the largest fraction of CD8+ cells (Fig. 2c). Subset V contained pDC which were identified by expression of the pDC-specific marker PDCA-1 (16) and Gr-1 and the absence of CD11b (17, 18). All subsets (I-V) described in BALB/c mice were found in similar frequencies in resistant B10.D2 and C57BL/6 mice (Fig. 2b and data not shown), although CD11b expression in both naive and infected B10.D2 was much lower compared with BALB/c and C57BL/6 mice (data not shown). Notably, frequencies of pDC (contained within subset V) were 2-fold higher in BALB/c compared with B10.D2 (Fig. 2d) and C57BL/6 mice (data not shown).
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We next tested the capacity of the CD11c+ subsets to present L. major Ag. To this end, the five populations were purified by cell sorting from draining lymph nodes of uninfected and 24 h-infected BALB/c mice and cultured with naive LACK-specific WT15 T cells. Strikingly, irrespective of the infection dose ranging between 104 and 106 parasites, subset II (CD11chighCD11bhigh) alone was capable to present Ag and induce T cell proliferation, whereas the other four subsets (I, III, IV and V) showed no activity, when compared with naive mice (Fig. 3a). Similar results were obtained at 48 and 72 h postinfection and comparing i.d. (ear) and s.c. (footpad) infection (data not shown). Moreover, similar to susceptible BALB/c mice, we found that subset II alone was responsible for Ag presentation in resistant B10.D2 mice (Fig. 3b). Low levels of IL-2 production induced by subsets I, III, and IV were insignificant compared with respective subsets from uninfected mice and due to usage of LMR7.5 hybridoma cells as responders, which showed a higher background activation compared with naive WT15 T cells. Importantly, subsets I-IV were roughly comparable in presentation of an irrelevant peptide (i.e., OVA323–339) added to cultures containing DO11.10 transgenic T cells (data not shown). Phenotypic analysis of CD11chighCD11bhigh cells revealed that a fraction of subset II cells acquired Gr-1 expression upon infection suggesting the recruitment of a novel cell population, which is possibly inflammatory blood monocytes undergoing differentiation to DC. Purification of Gr-1+ and Gr-1– cells by cell sorting and coculture with LMR7.5 cells showed that mainly Gr-1– cells presented L. major Ag and induced IL-2 production (Fig. 3c). In contrast, subset II Gr-1+ cells induced specific T cells poorly which may be explained by a more immature phenotype indicated by reduced expression of MHC class II (mean fluorescence intensity (MFI): 1328 ± 117 vs 3151 ± 526), CD86 (194 ± 18 vs 316 ± 33), and CD40 molecules (392 ± 19 vs 662 ± 92) compared with Gr-1– cells. CD11chighCD11bhigh (subset II) cells contained also a fraction of cells expressing the lymphoid marker CD8 (Fig. 2c). However, when L. major Ag presentation capacity of CD8+ and CD8– cells from subset II was compared, only CD8– but not CD8+ cells exhibited Ag presentation (Fig. 3d) indicating that L. major-presenting cells are myeloid DC.
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Skin-derived DCs are not responsible for early L. major Ag presentation in the lymph node
Previous work has shown that LC internalize L. major parasites and migrate to draining lymph nodes, where they stimulate specific T cells (7). However, we found that the population of L. major-presenting cells characterized above did not express langerin (Fig. 2c) or other LC-associated molecules such as gp40 and CD205 (data not shown) and therefore do not belong to LC, which dismisses a role of this population in initiation of immunity to L. major. In line with these findings, a recent publication showed that langerin mRNA was absent in DC harboring parasites in lymph nodes 3 days after infection (19). These results open the question whether DDC present L. major and initiate T cell responses. To address it, mice were infected with L. major parasites i.d. in the ears and the skin overlaying the infection site was painted with CMFDA, a green fluorescent dye, to label all epidermal and dermal cells (20). For comparison, ears were painted with an inflammatory skin irritant (i.e., DBP) together with CMFDA. Twenty-four hours later, draining lymph nodes were collected and analyzed for the presence of skin-derived cells, which were detectable as CMFDA+ cells lighting green.
Administration of CMFDA alone resulted in efficient labeling of both LC and DDC (data not shown) without inducing their migration to draining lymph nodes. When the CMFDA was administered together with a skin irritant, migration of skin-derived DCs was strongly induced as demonstrated by the appearance of a prominent population of CMFDA+CD11c+ cells in draining lymph nodes (1.05 ± 0.74% vs 0 ± 0.03 of total LN cells) which consisted mainly of DDC and no LC, as indicated by langerin staining (Fig. 4, a and b). Surprisingly, L. major infection resulted in poor migration of skin-derived cells (0.025 ± 0.01% CMFDA+ cells of total LN), which was 40-fold reduced compared with treatment with a skin irritant. However, combination of infection and application of irritant resulted in an increase rather than reduction in total numbers of migrated cells compared with irritant alone (58075 ± 8672 vs 36096 ± 16657).
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L. major APCs acquire soluble Ags drained through the conduits
It remains unclear how resident DC acquired parasite Ag in lymph nodes. One possibility is that the few skin-derived DC, which migrated from skin to lymph nodes during the first 24 h of infection, are transport vehicles for parasite Ag and deliver it to lymph node resident CD11chighCD11bhigh cells for uptake and presentation.
To test this hypothesis, mice were infected with L. major parasites in the ears and the site of infection was surgically removed 5 h after infection to prevent skin cells migration. Indeed, it has been shown that migration of skin-derived cells to draining lymph nodes requires longer than 14 h, while soluble proteins drain to lymph nodes within 2 h after s.c. injection, (11). Similarly, we observed that, upon skin painting, migrating cells required at least 10 h to reach draining lymph nodes, even when a skin irritant was applied (data not shown). Twenty-four hours after infection, CD11c+ cells from draining lymph nodes were isolated and tested for their ability to stimulate LMR7.5 cells, as compared with CD11c+ cells from lymph nodes draining an intact infection site. Irrespective of the removal of the site of infection, no significant difference was observed in the presentation of L. major Ag (Fig. 5a). Thus, acquisition of L. major Ag by CD11chigh CD11bhigh lymph node cells does not require migration of skin-derived DC.
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L. major presentation by resident DC is sufficient to prime specific T cells in vivo
We finally addressed the in vivo relevance of L. major Ag presentation by CD11chighCD11bhigh resident lymph node DC to specific T cells. Accordingly, CFSE-labeled LACK-specific naive CD4+ T cells were adoptively transferred into BALB/c mice. The recipient mice were then infected with L. major parasites in the ears and the infection sites were left intact or removed 5 h later to prevent migration of skin-derived cells. Five days after infection, activation of transferred T cells was evaluated by flow cytometry. Removal of the infection site did not affect division rate or activation of LACK-specific CD4+ T cells, as measured by down-regulation of CD62L and up-regulation of CD44 molecules (Fig. 5, c and d). Similar results were obtained comparing infection with 105 and 106 parasites, whereas no T cell proliferation was seen with inoculates of 103 parasites (data not shown). Thus, early L. major Ag presentation by resident CD11chighCD11bhigh DC occurs in vivo and is sufficient to prime L. major-specific T cells.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionDisclosuresReferences |
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Although a role of DDC in transport and presentation of L. major has not been investigated yet, two recent reports also questioned the importance of LC for immunity against L. major. Lemos et al. (8) have shown that genetically resistant mice lacking MHCII specifically on LC control L. major infection comparably to wild-type mice demonstrating that protective Th1 responses can develop in the absence of Ag presentation by LC. However, this model did not exclude a contribution of LC in transport and presentation of parasite Ag. Another study suggested that LC are not the principal APCs based on the absence of langerin mRNA in DC harboring parasites in draining lymph nodes 3 days after infection and proposed that DDC present L. major (19). Importantly, we showed that L. major Ag presentation in lymph nodes peaks around 24 h and wanes until 72 h before arrest until day 15 in a first phase of infection (Fig. 1). Therefore, studies between days 2 and 10 would possibly miss the main population presenting L. major.
Interestingly, we found that Ag presentation recommences between days 15 and 21 after infection (Fig. 1b) consistent with a previous report suggesting that a second wave of CD205+ cells carrying live parasites appears in the lymph nodes starting at day 5 (21). Interestingly, characterization of DC subsets during the second wave of infection (day 28) showed that the vast majority of cells corresponded to subsets II and IV and both were capable to present Ag. However, they did not express langerin ruling out LC (data not shown). Absence of subset I may be due to up-regulation of CD11c during the second wave so that these cells become CD11chigh and appear in subset II.
In addition to LC and DDC, which migrate from skin to lymph nodes under steady state conditions, various DC subtypes have been described in peripheral lymph nodes, including myeloid, lymphoid, and pDC. Absence of langerin and CD205 surface expression on CD11chighCD11bhigh cells presenting L. major Ag allowed us to exclude that these cells belong to LC and DDC, respectively (9, 10, 22). Furthermore, we showed that pDC do not present L. major. A considerable fraction of CD11chighCD11bhigh cells expressed CD8 molecule (Fig. 2c), suggesting they might be lymphoid DC. However, we and others showed that only the CD8– and not the CD8+ DC subpopulation was able to present L. major and activate specific T cells (Fig. 3d) (19).
Subset II (CD11chighCD11bhigh) cells, which slightly increased in numbers (2-fold) both in BALB/c and B10.D2 mice 24 h after infection, could be further subdivided in Gr-1+ and Gr-1– cells. In fact, we found that a population of Gr-1+ cells appeared in the draining lymph nodes upon infection, which are possibly inflammatory blood monocytes undergoing differentiation to DC upon tissue migration. However, these Gr-1+ cells showed a very poor capacity to activate specific T cells, although they expressed intermediate to high levels of MHCII molecules (Fig. 2c) and seemed to carry parasite Ag (as discussed below). In contrast, Gr-1–CD11chighCD11bhigh cells showed higher expression of costimulatory molecules and mediated L. major presentation (Fig. 3c). When infection was done in bone marrow chimeras generated by grafting CD45.2+ C57BL/6 mice with CD45.1+ bone marrow, subset II cells were found to exclusively express the donor marker, thus confirming a bone marrow origin (data not shown). Together, these results suggest that the DC population triggering the T cell response to L. major represents resident bone marrow-derived myeloid DC, which were already present in the lymph nodes at the time of infection.
The question remains of how these lymph node resident DC acquire parasite Ag from the skin. One possibility is through delivery by inflammatory monocytes (i.e., Gr-1+ in subsets I and II) that migrate to the lymph node upon infection. Indeed, although Gr-1+ cells were unable to present and activate specific T cells, they contained L. major Ag (data not shown) and therefore might act as Ag "transporters". However, further studies are necessary to clarify the origin and role of inflammatory monocytes.
Another possibility is that soluble Ag, released by live, damaged, or killed parasites in the skin, drains to lymph nodes through the lymph early after infection. In fact, in both susceptible and resistant mice, L. major Ag has been detected in draining lymph nodes starting from 4 h after infection as a gradient extending from the marginal sinus into the cortex (21). Recently, it has been reported that CD11c+CD11b+ resident DC are strongly associated with the reticular fibers of the conduit network, which enables them to rapidly acquire soluble Ag drained through the lymph into the conduits (11, 12). In favor of this possibility, our data provide evidence that the same DC population presenting L. major parasite Ag is also responsible for presentation of soluble OVA upon i.d. injection.
The chances for resident DC to acquire and present soluble Ag depends on parasite number and we found high presentation capacity of subset II with inoculates >105 parasites (Fig. 1c and data not shown), which is the dose conventionally used for experimental L. major infection. Inoculates containing 104-103 parasites required a high number of DC to observe T cell activation and seemed to be the threshold of detection in our system. It could be argued that the first wave of L. major presentation is a result of the high dose experimental model using >105 parasites and that the second wave reflects the physiology of natural infection. Indeed, even upon low dose infection, we cannot completely rule out that early presentation might be a consequence of Ag release by a fraction of noninfectious forms contaminating the inoculates. Interestingly, in this context, upon infection with 103 parasites, we did not observe Ag presentation in BALB/c mice at day 28 suggesting that the second wave commences later or that the parasites were efficiently controlled early after experimental low dose infection.
Recently, it has been reported that CD8+ DC rather than LC mediate activation of CTLs to skin herpes virus infection (23). Together with this, our finding raises the intriguing hypothesis that skin DC play a minor role in priming of T cells in response to skin pathogens ranging from viruses to complex parasites.
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Acknowledgments |
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Disclosures |
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Footnotes |
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1 This work was supported by Eidgenössische Technische Hochschule (Swiss Federal Institute of Technology) Research Grant TH-18/04-3. 
2 Address correspondence and reprint requests to Dr. Giandomenica Iezzi, Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistrasse 27, 8952 Zürich-Schlieren, Switzerland; E-mail address: iezzi{at}env.ethz.ch or Dr. Manfred Kopf, Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistrasse 27, 8952 Zürich-Schlieren, Switzerland. E-mail address: Manfred.Kopf{at}ethz.ch
3 Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DC; LC, Langerhans cell; DDC, dermal DC; i.d., intradermal; MHCII, MHC class II; CMFDA, 5-chloromethylfluorescein diacetate; LACK, Leishmania homolog for receptors of activated C kinase. DBP, dibutyl phtalate.
Received for publication October 11, 2005. Accepted for publication May 1, 2006.
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References |
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+ and CD11b+ dendritic cells is sufficient for control of Leishmania major. J. Exp. Med. 199: 725-730. - and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis. Eur. J. Immunol. 34: 1542-1550. [Medline]+ dendritic cells but not by Langerhans cells. Science 301: 1925-1928. This article has been cited by other articles:
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  A. Skallova, G. Iezzi, F. Ampenberger, M. Kopf, and J. Kopecky Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses J. Immunol., May 1, 2008; 180(9): 6186 - 6192. [Abstract] [Full Text] [PDF]
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L. Wang, L. S. Bursch, A. Kissenpfennig, B. Malissen, S. C. Jameson, and K. A. Hogquist Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions J. Immunol., April 1, 2008; 180(7): 4722 - 4727. [Abstract] [Full Text] [PDF]
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A. J. Wolf, B. Linas, G. J. Trevejo-Nunez, E. Kincaid, T. Tamura, K. Takatsu, and J. D. Ernst Mycobacterium tuberculosis Infects Dendritic Cells with High Frequency and Impairs Their Function In Vivo J. Immunol., August 15, 2007; 179(4): 2509 - 2519. [Abstract] [Full Text] [PDF]
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A. T. Shamshiev, F. Ampenberger, B. Ernst, L. Rohrer, B. J. Marsland, and M. Kopf Dyslipidemia inhibits Toll-like receptor-induced activation of CD8{alpha}-negative dendritic cells and protective Th1 type immunity J. Exp. Med., February 19, 2007; 204(2): 441 - 452. [Abstract] [Full Text] [PDF]
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