Biomedical subjects

M Röllinghoff

Publications and source records attributed to M Röllinghoff.

At least 73 records · Page 4Linked to original sources

PubMed1996

Intracellular murine IFN-gamma mediates virus resistance, expression of oligoadenylate synthetase, and activation of STAT transcription factors.

IFN-gamma is a pleiotropic cytokine that plays a major role in anti-infectious immune responses. The physiologic effects of IFN-gamma are thought to be mediated by the binding of extracellular IFN-gamma to its receptor at the cell surface, thereby triggering an intracellular signaling cascade. In this work, we present evidence for a completely intracellular mechanism for IFN-gamma to induce virus protection. Murine fibroblasts were transfected with the cDNA for murine IFN-gamma, and although no detectable amounts of IFN-gamma were released, these cells were resistant to lysis by the cytolytic vesicular stomatitis virus. In contrast to exogenously added IFN-gamma, the effect of the endogenously produced IFN-gamma was not abolished by treatment with neutralizing Abs. To test whether intracellular signal transduction occurs, an IFN-gamma variant was constructed with the carboxyl-terminal endoplasmic reticulum retention signal Lys-Asp-Glu-Leu (KDEL). Transfection of fibroblasts with this mutant IFN-gamma, anchored in the endoplasmic reticulum, led to virus resistance, thus demonstrating that biologic effects of this protein do not necessarily require binding to the receptor at the cell surface. However, the antiviral state induced by transfection with IFN-gamma-KDEL was strictly dependent on the presence of the IFN-gammaR, since fibroblasts derived from IFN-gammaR-deficient mice (IFN-gammaR -/-) were not rendered virus resistant. The virus resistance induced was accompanied by enhanced expression of 2'-5' oligoadenylate synthetase and constitutive activation of STAT1 (signal transducers and activators of transcription). Hence, autocrinous effects of IFN-gamma in cells naturally producing this cytokine might occur even in the absence of its secretion. The mechanisms involved in signaling appear to be identical with or closely related to those occurring after binding of IFN-gamma to its receptor at the cell surface.

2',5'-Oligoadenylate Synthetase↗

PubMed1996

Two distinct stimulus-dependent pathways lead to production of soluble murine interleukin-4 receptor.

The IL-4R exists in two forms, either membrane bound or as a soluble (s) molecule. Since the sIL-4R binds to its ligand with high affinity, thereby acting as an immunoregulatory molecule, we were interested in the processes leading to its release. First, the release of sIL-4R in the model of murine leishmaniosis was analyzed. Infection of mice with Leishmania major resulted in up-regulation of sIL-4R production by Ag-stimulated CD4+ T cells, with a maximum around 7 days after infection. To clarify the mechanisms underlying sIL-4R release, in vitro studies were performed. After stimulation of naive lymphoid cells with IL-4, sIL-4R release was dependent on up-regulation of spliced IL-4R mRNA, as shown by inhibition with specific antisense oligonucleotides. In contrast to this, no increase in the spliced IL-4R mRNA and no inhibitory influence of antisense oligonucleotides were observed after stimulation of T cells from IL-4-deficient mice with anti-CD3 mAb. Thus, TCR stimulation can lead to IL-4-independent sIL-4R production. Under these conditions proteolytic shedding of membrane-bound IL-4R appears to be the principal mechanism of release, since in contrast to stimulation with IL-4, iodinated sIL-4R could only be immunoprecipitated after cell surface labeling and subsequent TCR stimulation. The common gamma-chain, a component of the IL-4R complex, did not appear to be involved in the pathways leading to sIL-4R expression. This analysis suggests the existence of two differentially regulated pathways of sIL-4R release, possibly having different consequences for the regulation of IL-4 bioactivity.

Alternative Splicing↗

PubMed1996

Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase.

Nitric oxide (NO) synthase (iNOS) is required for the resolution of acute cutaneous leishmaniasis in resistant C57BL/6 mice. As is the case in several other infections, the clinically cured host organism still harbors small amounts of live Leishmania major parasites. Here, we demonstrate lifelong expression of iNOS at the site of the original skin lesion and in the draining lymph node of long-term-infected C57BL/6 mice. iNOS activity in the lymph node was dependent on CD4+, but not on the CD8+ T cells. By double labeling techniques, iNOS and L. major were each found in macrophages (F4/80+, BM-8+, and/or MOMA-2+) and dendritic cells (NLDC-145+), but not in granulocytes or endothelial cells. In situ triple labeling of lymph node sections revealed that approximately 30-40% of the L. major foci were associated with iNOS-positive macrophages or dendritic cells. The majority of the L. major foci (60-70%), however, was located in areas that were negative for both iNOS and the macrophage and dendritic cell markers. In L. major-infected C57BL/6 mice, which had cured their cutaneous lesions, administration of L-N6-iminoethyl-lysine (L-NIL), a potent inhibitor of iNOS, led to a 10(4)-10(5)-fold increase of the parasite burden in the cutaneous and lymphoid tissue and caused clinical recrudescence of the disease. Persistent expression of iNOS and resumption of parasite replication after application of L-NIL was also observed in resistant C3H/HeN and CBA/J mice. We conclude that iNOS activity is crucial for the control of Leishmania persisting in immunocompetent hosts after resolution of the primary infection. Failure to maintain iNOS activity might be the mechanism underlying endogenous reactivation of latent infections with NO-sensitive microbes during phases of immunosuppression.

Animals↗

PubMed1996

Expression and co-cytokine function of murine thioredoxin/adult T cell leukaemia-derived factor (ADF).

Human ADF (adult T cell leukaemia-derived factor), an isoform of thioredoxin, promotes proliferation of certain human lymphoid cell lines and is involved in many thiol-dependent reducing reactions. To study functional aspects of the murine homologue, we established inducible overexpression of murine ADF in E. coli and a purification method which led to an apparently homogeneous 14 kDa protein. This recombinant ADF was tested in proliferation assays with murine Th2 cells (D10.G4.1) and CTLL-2 cells. In synergy with IL-2, IL-4, IL-7 and IL-9 ADF displayed co-cytokine activity. These proliferative effects were neutralized by an affinity-purified polyclonal rabbit anti-ADF antiserum. The effects of ADF were critically dependent on the presence of 2-mercaptoethanol. Bacterial thioredoxin had similar effects on the proliferation of murine T cells. Thus, the thiol-related reducing capacity of these proteins is essential for their growth promoting activity. As investigated at the levels of mRNA and protein in several murine cell clones and lines as well as in mouse tissues ADF is expressed ubiquitously. Finally it could be demonstrated by competitive PCR that in contrast to cytokine mRNAs (e.g. IL-4 and IL-13) the expression of ADF mRNA in murine Th2 clones and spleen cells is not influenced by stimulation of these cells through the T cell receptor complex. Murine ADF therefore represents a protein constitutively expressed in a wide variety of cells with the capacity to enhance the proliferative effect of several cytokines on murine T cells.

Animals↗

PubMed1996

Invasion, control and persistence of Leishmania parasites.

Significant advances in research on the immunopathogenesis of leishmaniasis include the discovery of novel putative evasion and survival strategies of Leishmania parasites, a more detailed understanding of the function and regulation of interleukin-12, definition of molecules involved in cognate interaction between macrophages and T cells and new ideas concerning the mechanisms of host resistance and susceptibility. The use of transgenic mice for (re)probing certain immunological aspects of leishmaniasis has yielded not only predictable and confirmatory but also unexpected and pioneering results which require critical appreciation.

Animals↗

PubMed1996

Co-transfer of B cells converts resistance into susceptibility in T cell-reconstituted, Leishmania major-resistant C.B-17 scid mice by a non-cognate mechanism.

Resistance to infection of mice with Leishmania major parasites is dependent on the production of IFN-gamma by CD4+ T helper cells. C.B-17 scid mice, lacking both T and B cells, succumb very quickly to the infection, but develop resistance if reconstituted with appropriate numbers of T cells from BALB/c mice. In this model, we studied the role of B cells with regard to their ability to influence disease outcome and to function as antigen-presenting cells for T cells. For this purpose, we reconstituted scid mice (H-2d) with either T cells or with T and B cells obtained from (BALB/c x BALB.B)F1 mice (H-2d x b), and infected them with L. major parasites 1 day after reconstitution. Mice reconstituted with T cells alone cured the disease, whereas additional B cell reconstitution led to susceptibility. Healing was associated with a predominant Th1-type response. In all mice, L. major-specific T cell proliferation was restricted to the MHC phenotype of the recipient (H-2d) but not to that of the donor (H-2d x b), indicating that there was no detectable contribution of donor B cells in the priming of a T cell response. Furthermore, B cells, when purified from infected BALB/c mice, were unable to stimulate a L. major-specific CD4+ T cell clone (L1/1) without addition of exogenous antigen, in contrast to macrophages from the same animal. These data suggest that B cells, in vivo, do not carry L. major antigen in a form capable of activating specific CD4+ T cells. Therefore, B cells promote disease by means other than cognate interaction with CD4+ T cells.

Animals↗

PubMed1996

TCR- and IL-1-mediated co-stimulation reveals an IL-4-independent way of Th2 cell proliferation.

Previously, it has been shown that Th1 cells, when triggered solely via their TCR, are blocked from proliferation in response to IL-2. Herein, we describe a similar characteristic for Th2 cells in that immobilized mAb directed to the TCR blocked proliferation of Th2 cells in response to IL-4. This "proliferative block' was observed in all four Th2 cell clones tested, but not in a subline of one of the clones which has been cultured in vitro for several years. Addition of IL-1 neutralized the proliferative block in all four Th2 cell clones. Surprisingly, blocking experiments with sIL-4R and anti-IL-4 mAb revealed that in three out of four Th2 cell clones this effect of IL-1 was IL-4-independent and could also not be blocked by cyclosporin A (CsA). In contrast, the proliferation of one Th2 cell clone in response to the TCR- and IL-1-mediated signals was indeed inhibited by sIL-4R, anti-IL-4 mAb and CsA. Thus, our data illustrate that in addition to the well-known IL-4-dependent proliferation, there also exists an IL-4-independent, IL-1-mediated way of Th2 cell proliferation.

Animals↗

PubMed1995

Stable transfection of cloned murine T helper cells.

Here we describe a protocol for the stable transfection of murine T helper (Th) cells and long term culture of the resulting transfectants. The electroporation protocol was established for the murine Th2 clone L1/1 by testing different parameters determining the electric field (capacitance, voltage, single or twin pulse) as well as the activation status of the cells. The transfected T cells were genetically altered by stable integration of the neomycin resistance gene, encoded in the vector pM5neo, into the genome. For selection and long term culture of stable transfectants a scheme combining selection with the antibiotic neomycin (G-418, Geneticin) and repeated stimulation with antigen presenting cells (APC) and antigen was established. This protocol should also be applicable to other antigen reactive T cells. The resistance of the T cells to neomycin correlated directly with expression of the transferred neomycin resistance gene as demonstrated by mRNA analysis. Applying periodic reselection with neomycin the transfected Th2 cells were found to be stable for more than 18 months in culture and displayed an unaltered antigen recognition and lymphokine production pattern as compared with the untransfected L1/1 Th2 cells.

Animals↗

PubMed1995

2,4-Diamino-6-hydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis, downregulates the expression of iNOS protein and mRNA in primary murine macrophages.

2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, blocks the synthesis of tetrahydrobiopterin (BH4), which is a known cofactor of inducible nitric oxide synthase (iNOS). Previously, DAHP was shown to suppress the production of nitric oxide by cytokine-activated fibroblasts, smooth muscle cells or endothelial cells which could be attributed to its function as a cofactor antagonist. Here, we demonstrate that in interferon-gamma-activated murine peritoneal macrophages DAHP suppresses the expression of iNOS mRNA and protein in a BH4-independent manner and, thus, acts by a novel mechanism.

Amino Acid Oxidoreductases↗

PubMed1995

Neutralization of endogenous IL-6 suppresses induction of IL-1 receptor antagonist.

IL-1 is a potent cytokine that promotes host defense and inflammation. These processes may be modulated by an IL-1 receptor antagonist (IL-1Ra) that binds to and blocks IL-1 receptors. The objective of this study was to define the cellular origin and regulation of IL-1Ra production during bacterial infection. Oral infection of mice with Yersinia enterocolitica resulted in expression of IL-1Ra mRNA and synthesis of IL-1Ra in Peyer's patches (PP), the local site of infection, as well as in noninfected organs such as spleens. By immunostaining, recruited circulating neutrophils were identified to be the primary source of IL-1Ra in tissues. Only approximately 20% of the IL-1Ra-staining cells were accounted for by inflammatory macrophages. Strikingly, neutralization of IL-6 by anti-IL-6 antiserum caused a suppression of both IL-1Ra mRNA in PP and synthesis of IL-1Ra in circulating neutrophils. Confirmatory evidence that IL-6 participates in the generation of IL-1Ra was obtained when rIL-6 induced, and anti-IL-6 antiserum blocked, IL-1Ra expression in cultures of macrophage and polymorphonuclear leukocytes (PMN). These findings suggest that IL-6 induced induction of IL-1Ra may provide a negative feedback loop, facilitating resolution of the inflammatory response locally and presumably at remote sites of infection.

Animals↗

PubMed1995

Dendritic cells in Leishmania major-immune mice harbor persistent parasites and mediate an antigen-specific T cell immune response.

Upon infection with Leishmania major, a cause of human cutaneous leishmaniasis, mice of resistant strains are able to control the infection, with lesions resolving spontaneously. A long-lasting cell-mediated immunity protects them from reinfection. Nevertheless, small numbers of viable parasites persist in the lymph nodes of these mice. We have recently documented that, in addition to macrophages, epidermal Langerhans cells can ingest L. major. Furthermore, Langerhans cells have the unique ability to transport viable parasites from the infected skin to the draining lymph node for presentation to antigen-specific T cells and initiation of the cellular immune response. During migration, Langerhans cells develop into dendritic cells. In the present study, we analyzed whether dendritic cells support the persistence of parasites in immune hosts. Immunohistological studies and assays in vitro showed that in the lymph nodes of mice that have recovered from infection with L. major, both macrophages and dendritic cells harbor viable parasites. However, only dendritic cells were able to induce a vigorous T-cell immune response to L. major in vitro in the absence of exogenous antigen. Tracking experiments conducted in vivo suggested that the infected dendritic cells in the lymph nodes are derived from Langerhans cells that have emigrated from the skin. The data demonstrate that L. major-infected dendritic cells and macrophages in lymph nodes of immune animals represent long-term host cells, but only dendritic cells have the ability to present endogenous parasite antigen to T cells. Long-term infected dendritic cells may thus allow the sustained stimulation of a population of parasite-specific T cells, protecting the mice from reinfection. Our results favor the hypothesis that the persistence of antigen supports the maintenance of T cell memory and that dendritic cells are critically involved in this process.

Animals↗

PubMed1995

Early parasite containment is decisive for resistance to Leishmania major infection.

We investigated the early spread of Leishmania major in various mouse strains. In BALB/c mice, which are extremely vulnerable to L. major infection, the parasites disseminated within 10-24 h from the site of subcutaneous footpad infection in to the popliteal lymph node, spleen, lung, liver and bone marrow. Application of recombinant (r)IL-12 prior to infection prevented the early dissemination of parasites into visceral organs and the animals healed the infection. In three mouse strains tested, C57BL/6, CBA/J and C3H/HeJ, which are all resistant to L. major infection, the parasites remained localized in the footpad and in the draining LN for 3 days without evidence of dissemination. In C57BL/6 mice, depletion of NK1.1+ cells or neutralization of interferon (IFN)-gamma prior to infection led to rapid parasite spreading with kinetics similar to those seen in susceptible animals. Depletion of either CD4+ or CD8+ T cells in vivo prior to infection did not alter the kinetics of dissemination in any mouse strain tested. Experiments with severe-combined immunodeficient mice provided further evidence that parasite containment depends on natural killer cells and IFN-gamma, but is independent of T cells. The finding that all resistant mouse strains restrict the spread of the parasites within the first 24 h after infection strongly suggests that early parasite containment is closely associated with a resistant phenotype. The data show that local restriction of parasites in the pre-T cell phase of the infection is mediated by the innate immune system and suggest that this function plays an important role in the development of a protective T cell response.

Animals↗

PubMed1995

Lack of inducible nitric oxide synthase activity in T cell clones and T lymphocytes from naive and Leishmania major-infected mice.

Nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase (iNOS) is implicated in a number of immunological processes including killing of intracellular parasites, suppression of T cell proliferation, production of cytokines and destruction of tissue in autoimmune diseases. Considering that cytokine-activated mouse macrophages, fibroblasts and endothelial cells are potent producers of NO, we investigated whether T cells, as central participants in immune responses, can also be activated for the release of NO. Neither thymocytes nor type 1 or type 2 T helper cell clones generated significant amounts of nitrite (the stable end product of NO in culture supernatants) when stimulated by T cell mitogens, cytokines or antigen in the presence of irradiated antigen-presenting cells. Similarly, T cells freshly isolated from mice acutely infected with the intracellular pathogen Leishmania major did not produce NO upon restimulation in vitro. The lack of NO production was not due to the expression of enzymatically inactive iNOS, as we were unable to detect any iNOS protein in activated T helper clones or in freshly isolated T cells from infected mice by Western (protein) blot analysis. Finally, we tested whether iNOS expression in T cells might be restricted to a minor subpopulation and therefore only detectable on a single cell level. After immunofluorescence staining of lymph node or spleen cells from infected mice with antibodies against iNOS, F4/80- or Thy-1-antigen, macrophages, but no T cells, were found to express iNOS. Thus, we have no evidence that activated T helper cell clones or T cells from L. major-infected mice are high producers of NO.

Animals↗

PubMed1995

Protective effect of leflunomide on the natural course of Leishmania major-induced disease in genetically susceptible BALB/c mice.

Leflunomide has been reported as an immunomodulating agent which acts on a variety of cells including T- and B-lymphocytes. CD4+ T-lymphocytes are essential for the type of disease that develops after infection with the protozoan parasite Leishmania major. A variety of immunological interventions has been shown to modulate disease development. Therefore, the effect of leflunomide on the development of parasite-induced lesions and the ensuing immune response was investigated in genetically susceptible BALB/c mice. Oral feeding for 7 to 10 days of leflunomide (30 mg/kg per day) beginning 2 days prior to or at the day of infection led to the development of a stable resistant phenotype, i.e. to long-lasting (> 13 months) regression of the lesions and clinical cure. Starting leflunomide treatment 3 days after infection was ineffective. The main bioactive metabolite, 1726 B, did not inhibit viability or growth of L. major promastigotes and amastigotes in vitro. Quantitative analysis of CD4+ and CD8+ cells in spleens and lymph nodes of parasite-infected animals treated with leflunomide for 5 days showed no significant effect. In vitro, 1726 B dose-dependently inhibited growth of stimulated T-cells, which could not be restored by saturating amounts of exogenous IL-2 and IL-4. No effect was observed on the killing function of activated macrophages. Taken together, the data indicate that leflunomide is a potent prophylactic agent to prevent an otherwise lethal infection of BALB/c mice.

Animals↗

PubMed1995

CD44 plays a co-stimulatory role in murine T cell activation: ligation of CD44 selectively co-stimulates IL-2 production, but not proliferation in TCR-stimulated murine Th1 cells.

The murine CD44 receptor family is thought to be involved in a variety of lymphocyte functions, including lymphopoesis, lymphocyte homing and cell migration. Herein, we show that murine CD44 also plays a role as a co-stimulatory molecule for the activation of CD4+ T cells. Ligation of CD44 by mAb enhanced IL-2 production of long-term cultured, anti-CD3-stimulated Th1 cell lines. Moreover, anti-CD44 mAb synergized with anti-CD28 mAb in exerting this effect. A synergism of anti-CD28 and anti-CD44 mAb to co-stimulate IL-2 production was also observed in anti-CD3-triggered, freshly isolated splenic CD4+ T cells. Blocking experiments with cyclosporin A indicated that the intracellular pathways used by the CD28 and CD44 molecules appear to be different. In contrast to the effects on the IL-2 production of Th1 cells, neither anti-CD44 mAb alone nor the combination of anti-CD44 with anti-CD28 were able to induce proliferation of anti-CD3-triggered Th1 cells. In accordance, triggering of CD44 and/or CD28 by mAb was not sufficient to reverse the previously described 'proliferative block'. This term describes the unresponsiveness of Th1 cells against IL-2, which occurs when Th1 cells are triggered by anti-CD3 in the absence of co-signals. These data lead us to propose a model of Th1 cell activation which includes two functionally different types of co-signals: one for IL-2 production and a separate one for proliferation.

Animals↗

PubMed1995

Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression.

The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to encode a number of released Yersinia outer proteins that act as virulence factors by inducing cytotoxicity and inhibiting phagocytosis. This study demonstrates that one of the Yersinia outer proteins, the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNF-alpha), a macrophage-derived cytokine with central roles in the regulation of immune and inflammatory responses to infection. This conclusion is based on several lines of evidence. First, in macrophage cultures, suppression of TNF-alpha mRNA expression was induced by culture supernatant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-1 (IL-1) and IL-6, was induced by purified YopB. Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expression was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA. Finally, administration of anti-YopB antiserum to mice prior to infection with Y. enterocolitica increased TNF activity levels in Peyer's patches and coincided with a reduction in bacterial growth. The results thus provide direct evidence for a secreted eubacterial virulence factor that mediates selective suppression of TNF-alpha production. Although suppression of this single cytokine response is probably not sufficient to facilitate survival of the infecting organisms, the results suggest that suppression of TNF-alpha production by YopB significantly contributes to the evasion of Y. enterocolitica from antibacterial host defense.

Animals↗

PubMed1995

Stimulation of B-cell lymphopoiesis by interleukin-7 leads to aggravation of murine leishmaniasis.

The effect of recombinant interleukin-7 (IL-7) on the clinical course of murine leishmaniasis and the development of the accompanying immune response was investigated. Previously, IL-7 has been shown to possess stimulatory capacity for different cell types of the immune and haematopoietic system critically involved in the defence against Leishmania major (L. major), such as macrophages which are activated for the elimination of the parasite by IL-7. In contrast to these in vitro data, the present study indicates that treatment of genetically susceptible BALB/c mice with IL-7 at the onset of the infection leads to enhanced lesion development and a significantly accelerated death of the animals. This was correlated with a 40-fold increased parasite burden in spleens and lymph nodes. While the specific antibody response against L. major was not altered and lymphocytes of IL-7-treated mice produced comparable amounts of the T-helper type-2 (Th2) cytokines IL-4 and IL-10, less interferon-gamma (IFN-gamma) was measurable after antigenic stimulation of lymph node and spleen cells in vitro. One of the major changes appearing by the first week after infection in IL-7-treated mice was the increase of the total cell number in spleen and lymph nodes draining the local infection. Analysis of the cellular composition revealed that the enhanced cellularity was predominantly due to a rise in the B-cell compartment. Since antigen presentation by B cells has been implicated in the development of Th2 cells, the disease-aggravating activity of IL-7 is thought to be primarily due to augmentation of B lymphopoiesis.

Animals↗

PubMed1995

Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: enhanced lymphopoiesis with sustained lack of B1 cells and clinical aggravation of disease.

The Xid immunodeficiency was characterized by a total lack of B1 cells and reduced numbers and functions of B2 cells. In BALB.Xid mice, this defect results in an reduced susceptibility against infections with parasites such as Trypanosoma cruzi and Leishmania major. Since IL-7 acts on the B cell compartment by stimulation of pre-B cell proliferation, we analyzed the effect of recombinant IL-7 on L. major infection in BALB.Xid mice. After application of a single dose of IL-7 simultaneously with the infection, the clinical course in BALB.Xid mice was markedly aggravated, resembling that of normal BALB/c mice. IL-7-induced disease promotion was accompanied by an up to 100-fold higher parasite load in several tissues of these mice. When cytokine production of purified, L. major-specific CD4+ T cells from lesion-draining lymph nodes was examined, the IFN-gamma production seen in untreated BALB.Xid mice was suppressed in IL-7-treated animals. One of the major effects of IL-7 treatment in the lymphoid organs of BALB.Xid mice was the increase of the total number of B220, sIgM and MHC II-positive cells. These cells belonged to the B2 subset, since cells expressing surface molecules characteristic for B1 cells (Mac-1 and Ly-1) remained absent in spleens, lymph nodes and the peritoneum. In conclusion, selective up-regulation of B2 cells by IL-7 in the absence of B1 cells is associated with disease aggravation in L. major-infected BALB.Xid mice.

Animals↗