Capacity Of Antigen-presenting Cells Research Articles

Dendritic cells produce eicosanoids, which modulate generation and functions of antigen-presenting cells

Eicosanoids have been shown to be potent immunoregulatory arachidonic acid (AA) metabolites. AA is the precursor of prostaglandin E 2 (PGE 2) and leukotriene B 4 (LTB 4) which are able to modulate both inflammation and the immune response. Dendritic cells process and present antigens to T lymphocytes. They are highly specialized antigen-presenting cells (APC) and usually considered as ‘professional APC'. In the present paper, we report some data on the biosynthetic capacity of murine APC from the bone marrow (BM-DCs) to produce AA metabolites. Using an ELISA we have observed that BM-DCs spontaneously produce both PGE 2 and LTB 4 whose production increased in response to bacterial lipopolysaccharides (LPS). In addition we found that LTB 4 production was twice as high when both COX pathways were blocked with selective COX-inhibitors. We have also investigated the effect of PGE 2 and LTB 4 on the in vitro generation of the so-called BM-DCs. Exogenous PGE 2 and LTB 4 added to bone marrow cultures inhibit and promote, respectively, BM-DC generation. PGE 2 added to the maturing BM-DCs reduces their MHC class-II expression.

The Role of Antigen-presenting Cells in HIV Pathogenesis.

The study of antigen-presenting cells (APC) in HIV pathogenesis has been ongoing for almost 20 years. The initial studies recognized the important role of APC as targets for HIV infection and their ability to serve as reservoirs of virus, particularly in tissues. The issue of whether HIV impacts the functional competency of APC has been more controversial, with some studies showing reduced expression of important costimulatory molecules on APC, but others showing the functional capacity of APC to be normal. The study of APC has advanced with recent interest in one class of APC, namely the dendritic cell. These cells have been shown to consist of numerous subsets and serve an important role in bridging innate and adaptive immune responses. The impact of HIV infection on dendritic cells has recently been characterized, as well as the critical functional role of these cells in host defenses in HIV-infected patients. One of the more exciting recent advances in APC biology is the ability to manipulate APC ex vivo for therapeutic purposes in an attempt to restore immune responses in HIV-infected persons. This review covers many of the advances of the field of APC biology and puts them into perspective with HIV pathogenesis.

Cross-presentation of tumor antigens by bone marrow–derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression

Tumor antigen-specific T-cell tolerance may limit the efficacy of therapeutic cancer vaccines. Direct presentation of antigens by tumor cells incapable of providing adequate costimulation to tumor-specific T cells has been suggested as the basis for this unresponsiveness. Using parent-into-F1 bone marrow (BM) chimeras, this study unambiguously demonstrates that the induction of this tolerant state requires T-cell recognition of tumor antigen presented by BM-derived antigen-presenting cells (APCs), not tumor cells themselves. In the absence of host APC presentation, tumor-specific T cells remained functional, even in the setting of antigen expressed by B-cell lymphomas residing in secondary lymphoid tissues. The intrinsic APC capacity of tumor cells has therefore little influence over T-cell priming versus tolerance, a decision that is regulated at the level of host APCs. (Blood. 2001;98:1070-1077)

Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions.

Inflammatory mediators facilitate the maturation of dendritic cells (DC), enabling them to induce the activation, proliferation and differentiation of cognate T cells. The role of CD40 on DC and CD154 on T cells has been studied by the co-adoptive transfer of antigen-pulsed DC and TCR-transgenic (Tg) T cells in vivo. It is shown that in the absence of CD40-CD154 interactions, initial Tg T cell expansion occurs in vivo, but over time, T cell expansion cannot be sustained. The basis for the demise of the T cell population is likely due to the disappearance of the antigen-pulsed DC in the draining lymph nodes when CD154-CD40 interactions are interrupted. These findings show that both T cell and DC persistence in vivo is dependent on CD40-CD154 interactions. In addition to the physical persistence of the DC, CD40 triggering of DC also greatly increases the period for which they can productively present antigen to Tg T cells. Hence DC persistence and antigen-presenting cell capacity are both dependent on CD40 signaling. While TNF-alpha can mature DC as measured by a variety of criteria, the unique capacity of CD40 signaling to sustain T cell responses and induce DC maturation is underscored by the inability of TNF-alpha to rescue the immune deficiency of CD40(-/-) DC. Hence, the profound impact of CD154 deficiency on cell-mediated immunity may be due to its ability to limit the duration of antigen presentation in vivo and cause the premature demise of antigen-specific T cells.

Non‐steroidal anti‐oestrogens inhibit the differentiation of synovial macrophages into dendritic cells

Dendritic cells (DC) have been suggested to play an important role in the pathogenesis of rheumatoid arthritis (RA). Agents that inhibit DC differentiation and function may have a therapeutic value in the treatment of RA. To examine the effect of the non-steroidal anti-oestrogens toremifene and tamoxifen on the differentiation of synovial fluid (SF) macrophages into DC. SF macrophages from patients with RA were cultured with interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in the presence or absence of anti-oestrogens. The expression of cell surface markers on SF antigen-presenting cells (APC) was studied by flow cytometry. The capacity of SF APC to stimulate allogeneic T cells was studied using the mixed lymphocyte reaction. The production of tumour necrosis factor-alpha, IL-10 and transforming growth factor-beta1 was studied using ELISA. Anti-oestrogens inhibited the differentiation of SF macrophages into DC and the capacity of SF macrophage-derived DC to stimulate allogeneic T cells. By inhibiting the differentiation of SF macrophages into DC, non-steroidal anti-oestrogens may have beneficial effects in RA.

Parasite-Host Interaction: A New Point of View on Immune Regulation

A new hypothesis to explain the mechanism for the host immune system downregulation by the majority of parasitic organisms (Pr) so that it would recognize parasite antigenes (Pr-Ag) as selfantigenes has been suggested. The basis of the advanced hypothesis is the capacity of antigen-presenting cells (APC) to suppress the activity of T and B lymphocytes if they recognize the Pr-Ag, which is synthesized inside the APC. Two main ways and the intermediate one of the Pr-specific host immunity reaction dowregulation have been put forward within the framework of the above hypothesis: 1) noncellular Pr release self-mRNAs to change the host immune system 2) an APC intracellular Pr makes the Pr-Ag cell-host tolerant with the help of self-Ags and/or self-mRNA 3) the intermediate way: the non-APC intracellular Pr secrete self-mRNRs through the host cell membrane to the APC. Similarities existing between the capacity of Pr to downregulate host immunity, on the one hand, and the immunosuppressive properties of the place...

Thiol-mediated redox regulation of intestinal lamina propria T lymphocytes.

Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor-ligand interactions represents a critical parameter for proliferation of LP-Ts. The availability of cysteine is limiting for the intracellular production of glutathione, which in turn is essential for cell cycle progression. When cysteine is provided either directly or by addition of the reducing agent 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocytes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cysteine, and thereby secure physiological unresponsiveness to antigen exposure in the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD.

‘Anergic’ T cells Modulate the T-cell Activating Capacity of Antigen-presenting Cells

Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called ‘anergic’ T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that ‘anergic’ T cells mediate this suppressive effect via modulation of the T-cell activating capacity of the antigen-presenting cell (APC). Upon removal of the ‘anergic’ T cells, the suppressive APC phenotype persisted, indicating that ‘anergic’ T cells conditioned the APC to become a mediator of T cell suppression. The inhibitory signal delivered by ‘anergic’ T cells depended on the presence of the cognate ligand for the ‘anergic’ T cell, and appeared to be dominant since previously activated APC were rendered inhibitory as well. These findings imply that APC upon cross-talk with T cells can adopt distinct functional phenotypes ranging from T-cell stimulatory to T-cell suppressive. The contribution of ‘anergic’ T cells to the functional tuning of APC offers an explanation for the maintenance of ‘anergic’ T cells in the repertoire, and for their role in immunoregulation.

Immunosuppression photo-induite et cancers cutanés

The increased incidence of skin cancers is due to modifications of our behavior toward solar exposure. Photocarcinogenesis represents the sum of complex and intricate events that lead to the occurrence of skin cancers. In epidermal cells UV light induces lesions of DNA that lead to modifications in oncogene and tumor suppressor gene expression. UV-induced immunosuppression is also important for tumoral promotion. UV exposure decreases the number of Langerhans cells in the epidermis and modifies their antigen-presenting cell capacity. Numerous experimental data obtained in animal models clearly indicate the existence of a relationship between UV-induced immune suppression and skin cancers. In humans, growing evidence suggests that skin cancers and photoimmunosuppression are linked. Better knowledge of mechanisms involved in UV-induced immune suppression is essential for developing new strategies aimed at photoprotection and cancer prevention.

Internalization of Iscom-Borne Antigens and Presentation under MHC Class I or Class II Restriction

Exogenous nonreplicating antigens (Ag) incorporated into immunostimulating complexes (iscoms) induce CTL responses under MHC class I restriction. A requirement for inducing CTL responses is that the Ag is delivered to the cytosol of antigen-presenting cells (APC), a route restricted to endogenously produced Ag. To investigate the mechanisms by which iscoms elicit MHC class I-restricted responses, the intracellular distribution of influenza virus envelope proteins incorporated in iscoms (flu-iscoms) or in micelles (flu-micelles) was studiedin vitrousing murine peritoneal cells (PEC). Ultrathin sections of cells pulsed with biotinylated flu-iscoms or flu-micelles were analyzed by electron microscopy after detection of the biotin label by reaction with streptavidin–gold. PEC pulsed with flu-iscoms showed a pattern of scattered gold particles distributed in clear and dense vesicles as well as in the intracellular space but not associated with organelles. In cells pulsed with flu-micelles, Ag was also detected in most cellular compartments but at a considerably lower concentration. The intracellular distribution of particulate Ag in iscom or micelle form was confirmed by lysis and differential centrifugation of Ag-pulsed APC. Furthermore, P815 cells pulsed with flu-iscoms were lysed by specific immune effectors showing that the iscom-Ag was processed and presented by class I-expressing APC. Flu-iscoms were internalized about 50-fold more efficiently than ovalbumin iscoms (ova-iscoms) suggesting that the nature of the protein and/or the presence of cellular receptors are important factors influencing the capacity of APC to take up iscom-borne proteins. PEC accounted for the most active internalization of iscom-borne Ag, although splenic dendritic cells and B cells also took up flu-iscoms with remarkable efficiency.

Targeting a polyepitope protein incorporating multiple class II-restricted viral epitopes to the secretory/endocytic pathway facilitates immune recognition by CD4+ cytotoxic T lymphocytes: a novel approach to vaccine design.

The role of CD4+ and CD8+ cells in the generation of an effective immune response against viral infections is well established. Moreover, there is an increasing realization that subunit vaccines which include both CD4+- and CD8+-T-cell epitopes are highly effective in controlling viral infections, as opposed to those which are designed to activate a CD8+- or CD4+-T-cell response alone. One of the major limitations of epitope-based vaccines designed to stimulate virus-specific CD4+ T cells is that endogenously expressed class II-restricted minimal cytotoxic-T-lymphocyte (CTL) epitopes are poorly recognized by CD4+ CTLs. In the present study we attempted to enhance the efficiency of class II-restricted endogenous presentation of minimal class II-restricted CTL epitopes by specifically targeting a polyepitope protein to class II processing compartments through the endosomal and/or lysosomal pathway. A significantly enhanced stimulation of virus-specific CD4+-T-cell clones by antigen-presenting cells (APC) expressing the recombinant polyepitope protein targeted to the endocytic/secretory pathway was readily demonstrated in cytotoxicity assays. In addition, in vitro activation of Epstein-Barr virus- and influenza virus-specific CD4+ memory CTLs by the recombinant constructs encoding the polyepitope protein, specifically targeted to the lysosomal compartment, was also demonstrated. The enhanced stimulatory capacity of APC expressing a lysosome-targeted polyepitope protein has important implications for vaccine design.

Analysis of Neonatal T Cell and Antigen Presenting Cell Functions

ABSTRACT: Neonates are more susceptible to infection than adults and exhibit more intense or prolonged clinical symptoms. The extent to which deficiencies in T cell or antigen presenting cell (APC) function underlie hyporesponsiveness is incompletely understood. Here, immune function of cord blood mononuclear cells (CBMC) from healthy, full-term neonates was compared with adult PBMC. As widely reported, polyclonally-stimulated T cell proliferation was found to be equivalent, while IFNγ responses were markedly lower amongst neonates. Reasoning that such stimuli may elicit responses qualitatively different from those that would be obtained following MHC-dependent, cognate T cell activation, alloantigen-specific responses were evaluated. Strikingly, neonates exhibited IFNγ, IL-4 and IL-10 production equal to adults in short term primary culture. Both the frequency (Fisher’s p < 0.0004) and intensity (<7.5 vs 36.5 pg/ml; Wilcoxon P = 0.005) of alloantigen stimulated IL-5 responses were elevated among neonates, a finding equally evident using irradiated adult or neonatal cells as stimulators. Finally, the relative capacity of neonatal APC as stimulators of cytokine synthesis was assessed by a novel approach using CBMC as both responders and stimulators in MLR. Irradiated neonatal cells consistently stimulated similar proliferative but substantially lower IFNγ responses than did adult APC, independent of responder origin. The data argue; (i) T cells are largely immunocompetent at birth, (ii) accessory cell function is not fully mature, and (iii) the widely observed hyporesponsiveness to pathogens may be primarily due to immaturity of APC function or costimulator molecule expression.

Epidermal Dendritic Cells Induce Potent Antigen-Specific CTL-Mediated Immunity

Professional antigen-presenting cells (APCs) are required for the initiation of an immune response. Dendritic cells (DCs) are the most potent APCs identified thus far and can present antigen in the context of co-stimulatory signals required for the stimulation of both primed and naïve T cells. Cytotoxic T lymphocytes (CTLs) are critical to the immune response against tumors or virally infected cells. Optimal stimulation of antigen-specific CTLs is the goal of evolving immunization strategies for the prevention or therapy of viral infections and tumors. Epidermal dendritic cells (eDCs), or Langerhans cells, can present antigens for the stimulation of CD4+ T cell dependent anti-tumor immunity and may play a role in tumor surveillance. The capacity of eDCs to induce tumor-specific CD8+ CTL immunity has not been determined. We have previously shown that DCs derived from bone marrow precursors (BmDCs) under the influence of cytokines can induce protective, antigen-specific CTL-mediated anti-tumor immunity. Here we show that subcutaneous immunization with ovalbumin (OVA) peptide (SIINFEKL(257-264))-pulsed eDCs induced OVA-specific, CD8+ CTLs that lyse the OVA-expressing target. Furthermore, mice vaccinated with OVA peptide-pulsed eDCs were completely protected from subsequent challenge by the OVA-expressing melanoma MO5. The capacity of peptide-pulsed eDCs to induce CTL-mediated immunity is directly dependent on the dose of eDCs administered. Importantly, the APC capacity of eDCs is comparable to that of BmDCs, as mice immunized with eDC populations containing at least as many class II+/B7.2+ cells as populations of BmDCs were equally protected against challenge with MO5. These results demonstrate that eDCs can be potent inducers of antigen-specific CD8+ CTL-mediated immunity. They suggest that eDCs may be important targets for antigen delivery strategies aimed at inducing antiviral or anti-tumor immunity.

Enhanced functional capacity of the peritoneal macrophages as antigen presenting cells after aclacinomycin treatment in mice

Aclacinomycin (ACM) is an oncostatic of the anthracycline family, largely used in patients and experimentally in mice. ACM has been reported to enhance phagocytosis, secretion of free oxygen radicals and of interleukin 1. Its injection is also followed by an increase of the cytotoxic and cytostatic activity of murine peritoneal macrophages. In the present work we investigated whether ACM modifies the antigen-presenting cell capacity of murine peritoneal macrophages. Purified T lymphocytes were cultured with peritoneal macrophages from either normal or ACM treated mice (4 mg/kg day -4) which were previously incubated with phytohemagglutinin. The T cell proliferative response was greater in cultures with normal macrophages, indicating that macrophages from ACM-treated mice had a better antigen presenting activity than normal untreated macrophages.

Antigen presentation by autoreactive proteolipid protein peptide-specific T cell clones from chronic progressive multiple sclerosis patients: roles of co-stimulatory B7 molecules and IL-12

To assess the role of T cell antigen (Ag) presentation in multiple sclerosis (MS), proteolipid protein (PLP) peptide reactive CD4 + T cell clones (TCCs) from MS patients and normal subjects were studied. TCCs derived from chronic progressive (CP) MS patients were able to proliferate and secret cytokines in response to PLP peptide stimulation in the absence of professional antigen presenting cells (APCs), suggesting that these T cells can simultaneously present and respond to Ags. However, they did not respond to total PLP protein, suggesting that PLP-peptide TCCs were unable to process and present the whole PLP molecule. The ability of the different TCCs to act as APCs in response to Ag stimulation did not correlate with expression of HLA-class II molecules. However, the degree of expression of B7-1 and B7-2 co-stimulatory molecules showed a significant correlation with APC capacity. Furthermore, a combination of anti-B7-1 and anti-B7-2 mAbs effectively inhibited proliferative responses as well as secretion of IL-10, IFN γ and TGF β induced by antigen presenting T cells. By contrast, IL-4 secretion was not affected. Finally, IL-12 significantly enhanced the efficiency of T cell Ag presentation by a pathway independent of Ag processing, suggesting that IL-12 might act as an additional co-stimulatory signal for T cell activation during T–T cell interactions. Together, these observations suggest that Ag presentation by T cells might amplify and perpetuate an autoimmune response previously initiated by professional APCs. These properties may account for progression of MS into a CP phase.

Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection.

Recent data implicates a role for the CD40-CD40 ligand (CD40L) pathway in graft rejection. One potential mechanism is direct costimulation of T cells through CD40L. Alternatively, the ability of CD40 stimulation to induce CD80 (B7-1) and CD86 (B7-2) expression on antigen-presenting cells (APCs) has led to the hypothesis that the role of CD40-CD40L interactions in transplant rejection might be indirect, i.e., to promote the costimulatory capacity of APCs. Here, we have used a murine vascularized cardiac allograft model to test this hypothesis. Treatment of the recipients with donor splenocytes and a single dose of anti-CD40L mAb induces long-term graft survival (> 100 days) in all animals. This is associated with marked inhibition of intragraft Th1 cytokine [interferon gamma and interleukin (IL) 2] and IL-12 expression with reciprocal up-regulation of Th2 cytokines (IL-4 and IL-10). In untreated allograft recipients, CD86 is strongly expressed on endothelial cells and infiltrating mononuclear cells of the graft within 24 hr. In contrast, CD80 expression is not seen until 72 hr after engraftment. Anti-CD40L mAb has no detectable effect on CD86 up-regulation, but almost completely abolishes induction of CD80. However, animals treated with anti-CD80 mAb or with a mutated form of CTLA4Ig (which does not bind to CD86) rejected their cardiac allografts, indicating that blockade of CD80 alone does not mediate the graft-prolonging effects of anti-CD40L mAb. These data support the notion that the role of CD40-CD40L in transplant rejection is not solely to promote CD80 or CD86 expression, but rather that this pathway can directly and independently costimulate T cells. These data also suggest that long-term graft survival can be achieved without blockade of either T cell receptor-mediated signals or CD28-CD86 engagement.

TGF-β1 pretreatment impairs the allostimulatory function of human bone marrow-derived antigen-presenting cells for both naive and primed T cells

Transforming growth factor-beta (TGF-β) exhibits strong antiproliferative effects upon lymphocytes and inhibits many of the effector functions of activated immune cells. However, its influence on the inductive phase of immune responses, and in particular its effect on antigen-presenting cells (APC), has not been well studied. In this investigation, we examined the influence of human TGF-β1 on the antigen-presenting function of human bone marrow (BM)-derived APC propagated in liquid culture for 11–17 days in response to granulocyte/macrophage colony-stimulating factor (GM-CSF). These cells were predominantly macrophage, accompanied by a minor population of dendritic cells. TGF-β1 had no effect upon the allostimulatory function of vertebral body whole BM cells cultured for 3–5 days in GM-CSF. However, it markedly reduced the allostimulatory capacity of BM-derived APC exposed to the cytokine for the last 3 days of culture. This inhibitory action could not be ascribed to cytokine ‘carry-over’, or to any consistent changes in the expression of cell surface molecules implicated in antigen presentation (HLA-DR), intercellular adhesion (ICAM-1; CD54), or costimulatory activity (B7-1; CD80). Mechanisms that may underlie the inhibitory action of TGF-β on APC function and the immunologic and possible clinical implications of the findings are discussed.

Antigen presentation in allergic sensitization.

IgE antibodies, when cross-linked by allergen on the surface of effector cells such as mast cells and basophils, are known to be directly responsible for immediate type hypersensitivity reactions. In addition, IgE may be involved in other, indirect, mechanisms, fundamental to the pathogenesis of allergic diseases, such as enhancement of the antigen capturing capacity of antigen presenting cells. IgE mediated antigen presentation could lead to a continuous activation of the immune system by very low concentrations of allergen. As a result, Th2 cell populations may expand and may induce more B cells to switch to IgE production. Subsequently, the overproduction of IgE and Th2 cells in a patient may explain the clinical observation that certain allergic patients deteriorate from sensitivity to a single group of allergens to sensitivity to multiple groups of allergens. Therefore, control of IgE production is not only important for the treatment of allergic symptoms, but may also regulate deterioration of allergy via the mechanism of CD23/IgE mediated allergen presentation by naive B cells. The role that monocytes, which have recently been found to express Fc epsilon RI, play in the pathogenesis of allergy, remains speculative. We hypothesize that their role may be to remove IgE from the circulation and re-direct the immune response from naive B cells. IgG antibodies which cannot be used for antigen uptake by B cells also direct the immune response to monocytes.

Donor antigen-presenting cell-independent rejection of islet xenografts.

Donor-derived antigen-presenting cells (APC) are thought to serve as major stimulators for triggering the rejection of tissue allografts. However, the capacity of APC to stimulate xenogeneic T cells is generally deficient relative to the corresponding response from allogeneic T cells. For this reason, the contribution of donor-type APC to xenogeneic graft rejection remains unclear. Using a concordant species combination (rat to mouse), we examined the requirement for donor-type APC in triggering islet xenograft rejection. While the depletion of donor-type APC resulted in indefinite allograft survival, similar depletion of APC from xenogeneic rat islets resulted in only modest graft prolongation. Furthermore, APC-depleted rat xenografts were rejected by a CD8+ T cell-independent mechanism, as determined by appropriate depletion of T cell subsets through monoclonal antibody therapy. This contrasts with the dependence of islet allograft rejection on both CD4+ and CD8+ T cells. Although in vitro experiments show that rat APC can directly stimulate mouse T cells, rat APC do not appear to be required for xenograft immunity in vivo. We conclude that the mechanisms of islet allograft and xenograft rejection differ both in the dependence on donor-type APC and in the role of T cell subsets in the response.

Mechanism of enhanced antigen presentation by B cells activated with anti-mu plus interferon-gamma: role of B7-2 in the activation of naive and memory CD4+ T cells.

B cells activated with anti-mu antibody plus interferon (IFN)-gamma exerted strong antigen presentation activity for T cell proliferation. The enhanced antigen presentation function was shown to be due to the increase in B7-2 expression. When B cells were stimulated with anti-mu, expression of MHC major histocompatibility complex class II, heat-stable antigen (HSA), ICAM-1 and B7-2 was increased. The presence of IFN-gamma further augmented the expression of B7-2 on anti-mu-stimulated B cells. B7-1 was not expressed on B cells under these conditions. The participation of B7-2 in the elicitation of the proliferative response of T cells was confirmed by the inclusion of anti-B7-2 antibody in cultures. The enhanced expression of either HSA or ICAM-1 was shown not to play a major role in the increased B cell antigen presentation capacity. The major T cell population responding to this activated B cell antigen presentation was shown to be CD44low naive CD4+ T cells, whereas CD45RBlow memory CD4+ T cells responded only weakly. The difference in proliferative responses between naive and memory CD4+ T cells was explained by the different efficiency in IL-2 production of these cell populations in response to antigen presentation by B cells activated by anti-mu plus IFN-gamma. These results suggest that IFN-gamma plays an important role in recruitment of naive T cells for an immune response.