Tonsillar B cells do not express PSGL-1, but a significant fraction displays the cutaneous lymphocyte antigen and exhibits effective E- and P-selectin ligand activity.

Skin-homing T cells are defined by the expression of the cutaneous lymphocyte-associated antigen (CLA) which enables the cells to selectively bind to vascular endothelial E-selectin close to sites of cutaneous inflammation, an initial step in the effective extravasation from blood into the inflamed tissue. Essentially all CLA on T cells decorates the backbone of the P-selectin glycoprotein ligand-1 (PSGL-1). In this study we show that human peripheral blood B cells (PBBC) and tonsillar B cells (TBC) do not display PSGL-1 in fluorescence-activated cell sorter analysis using different murine monoclonal antibodies and polyclonal rabbit anti-PSGL-1 antiserum.

Neutrophils, monocytes, and dendritic cells express the same specialized form of PSGL-1 as do skin-homing memory T cells: cutaneous lymphocyte antigen.

Memory T cells in inflamed skin express the cutaneous lymphocyte-associated antigen (CLA), a glycosylated epitope defined by the mAb HECA-452. We previously reported that on T cells, CLA occurs almost exclusively on the protein backbone of P-selectin glycoprotein ligand-1 (PSGL-1). T cells exhibiting the CLA isoform of PSGL-1 can tether and roll on both E- and P-selectin, while T cells expressing PSGL-1 without the CLA epitope do not bind E-selectin, though they may bind P-selectin.

Functional cutaneous lymphocyte antigen can be induced in essentially all peripheral blood T lymphocytes.

The cutaneous lymphocyte-associated antigen (CLA) is a skin-homing receptor expressed on a minority of memory-type peripheral blood T (PBT) lymphocytes. Induction of high-level CLA expression in PBT has previously been difficult to accomplish in vitro. Here we report that constitutive CLA expression could be readily induced in virtually all PBT by various polyclonal activators.

Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells.

T cells play a pathogenic role in many inflammatory and certain malignant skin diseases, including psoriasis, atopic and allergic contact dermatitis, and cutaneous T-cell lymphoma. Memory T cells that infiltrate the skin express a unique skin-homing receptor called cutaneous lymphocyte-associated antigen (CLA), a carbohydrate epitope that facilitates the targeting of T cells to inflamed skin. CLA is defined by both its reactivity with a unique monoclonal antibody, HECA-452, and its activity as a ligand for E-selectin, but the structure of the protein component of CLA has not previously been defined.

Induction of cognate and non-cognate T-cell help for B-cell IgE production in relation to CD40 ligand expression.

Nonactivated, fixed peripheral blood T cells (PBT) from healthy donors or patients with X-linked-hyper-IgM (HIGM) syndrome, or cloned T cells provided effective help for tonsillar B lymphocytes for induction of IgE or other immunoglobulin (Ig) isotypes. Helper activity was mediated by staphylococcal superantigens adsorbed to the T cells prior to fixation and required presence of IL-4 in the cultures. We demonstrated that the T cells neither expressed detectable CD40 ligand at the beginning of the superantigen treatment nor 24 h later.

Induction of IgE and IgG1 in human B cell cultures with staphylococcal superantigens: role of helper T cell interaction, resistance to interferon-gamma.

Non-antigen-specific activation of human B lymphocytes for IgE production in vitro requires the presence of interleukin 4 and non-cognate physical interaction with T cells. The latter can be replaced by antibodies directed against the B cells' CD40 structure. Antigen-specific induction of immunoglobulin responses, including IgE, is difficult in human lymphocyte cultures.

Phorbol ester, prostaglandin E2, forskolin and okadaic acid differentially modulate interleukin-4-versus interleukin-2-dependent immunoglobulin induction in human cellular models, in contrast to other selected modifiers of cellular activation.

Interleukin 2 (IL2) and 4 (IL4) are the most important mediators for immunoglobulin (Ig) synthesis of human B lymphocytes. There is no obvious difference with regard to Ig isotypes induced by either lymphokine except for IgE: only IL4 induces this allergic antibody type. Monoclonal anti-CD40 antibodies enhance both IL2- and IL4-dependent Ig induction.

Recombinant interleukin 2 rapidly augments human natural killer cell activity.

Recombinant human interleukin 2 (r-IL-2) rapidly stimulated human natural killer cell activity in vitro. Augmentation of NK activity occurred within 1 hr of preincubation with r-IL-2. Responsive killer cells were typical NK cells as shown by cell fractionation procedures.

In vivo activation of murine natural killer cell functions by human recombinant DNA interleukin 2.

Intraperitoneal (i.p.) injections of purified human recombinant DNA (rDNA)-interleukin 2 (IL 2) resulted in in vivo activation of local natural killer (NK) cell activities in wild-type and congenitally athymic mice.

Modulation by cyclosporin A of murine natural resistance against herpes simplex virus infection. I. Interference with the susceptibility to herpes simplex virus infection.

Adult BALB/c mice which are medium-high resistant against intraperitoneal (i.p.) infection with herpes simplex virus type 2 (HSV-2) manifested a drastic increase in susceptibility to the virus when treated locally with cyclosporin A (CyA) during infection.

Studies on the interrelation of resistance and immunity in a mouse model system of herpes-simplex type 2 infection.

Intraperitoneal (i.p.) vaccination of mice with attenuated herpes simplex virus type 2 (HSV 2) induced solid protection to i.

Modulation by cyclosporin A of murine natural resistance against herpes simplex virus infection. II. Influence on the HSV-induced natural killer cell responses, macrophage activities and interferon levels.

Cyclosporin A (CyA) interfered locally at the site of injection with several resistance functions which are of potential importance in experimental herpes simplex virus (HSV) infections of mice. HSV-induced stimulation of macrophage phagocytosis was reduced by CyA when the mice were infected 5 days before the assay. The in vitro replication of the virus in macrophages, however, was enhanced.

Evaluation of live and inactivated influenza A virus vaccines in a mouse model.

Induction of cross-protective immunity against serologically distinct subtypes of influenza A virus in mice was examined in an attempt to correlate cross-protection with heterotypic lymphocyte responses. Live and inactivated virus vaccines protected against the homologous subtype, but only whole virus protected against heterologous subtypes. Live virus vaccines provided better cross-protection than inactivated virus vaccines.

Experimental infection of inbred mice with herpes simplex virus. IV. Comparison of interferon production and natural killer cell activity in susceptible and resistant adult mice.

Inbred mouse strains differ in susceptibility to infection with herpes simplex virus type 1 or type 2 (HSV-1, HSV-2). In this study interferon production was tested in the peritoneal exudate of mice after intraperitoneal (i.p.

Killer T cell responses to influenza A during a drift period: studies in mice.

After intravenous immunization of mice with any influenza A H3N2 drift strain attempts to restimulation of cytotoxic T cell (CTL) activities with the same virus or other drift period variants were unsuccessful for up to 6 weeks. Cross-stimulation 4-5 months after primary sensitization yielded, in most situations, positive but lower--as compared to primary--secondary cytotoxic T cell responses. Homotypic challenge was also effective after priming with some influenza A subtypes (A/E/72, A/PC/73, A/T/77) at this time.

Selective induction of immunological tolerance in antiviral T killer cells of inbred mice after treatment with cyclosporin A.

Primary anti-influenza A cytotoxic thymus-derived (T) and bone marrow (B) lymphocyte-dependent responses in inbred mice were used as an in vivo model system to study the effects of the immunosuppressive fungus metabolite cyclosporin A (CyA). Five consecutive daily oral applications of CyA, with the first being given 1 or 2 h before virus inoculation of the animals, caused a complete blockage of induction of anti-influenza T killer cells and a partial reduction of cytotoxic B lymphocyte activities. Adoptive cell transfer experiments revealed that incapability to respond was due neither to humoral factors nor to the generation of suppressor cells.

In-vivo modulation of macrophage functions by herpes simplex virus type 2 in resistant and sensitive inbred mouse strains.

Intra-peritoneal (i.p.) infection of mice with herpes simplex virus type 2 (HSV 2) attracted macrophages into the peritoneum.

Induction of natural killer cells by herpes-simplex virus type 2 in resistant and sensitive inbred mouse strains.

Infection of mice with herpes simplex virus type 2 (HSV 2) stimulated natural killer (NK) cells in a variety of inbred mouse strains including athymic nude mice. Essentially all mouse strains tested exhibited high NK activity on day four after virus inoculation. Assayed 24 hours after infection, SWR/J, AKR/J, SJL/J and C57B1/10J mice were low or negative for these non-virus-specific cytotoxic responses.

Function, target-cell preference and cell-surface characteristics of herpes-simplex virus type-2-induced non-antigen-specific killer cells.

Wild-type and congenitally athymic nude mice injected with herpes-simplex virus type 2 (HSV 2) responded with a local outburst of non-antigen-specific killer cells masking any virus-specific response. Cytolytic activity could be assayed on mouse-tumor cell lines and on syngeneic or allogeneic non-transformed cells from various sources. Some of the tumor cell lines and proteose-peptone-induced peritoneal exudate cells were lysed more efficiently after infection with either HSV 2, vaccinia or influenza A virus.

Induction of cytolytic T- and B-cell responses against influenza virus infections.

Inoculation of mice with live influenza virus results in the induction of cytotoxic thymus-derived (T) lymphocytes and of bone marrow-derived (B) cells producing antiviral antibodies. An assay system was developed to evaluate both types of immune responses on a cellular basis within the same lymphocyte pool with no need to separate out the different effector cell classes. The test system represented a modification of the 51Cr-release assay.

The role of histocompatibility gene products in lymphocyte triggering and differentiation.

Studies performed both in vivo and in vitro have demonstrated that genetic restrictions exist in the development of optimal cell-cell interactions in the immune system. Thus, in mice, the presence or absence of gene identities in the I region of the H-2 complex determines the capacity of lymphoid cells to interact. These cell interaction or CI genes appear to code for cell surface molecules integrally involved in regulatory cell interactions.

Activation of T and B lymphocytes in vitro: presence of beta2-microblobulin determinants on allogeneic effect factor.

The biologically acitve entity termed allogeneic effect factor, which is produced by alloantigen-activated T cells and has been shown to regulate triggering and differentiation of B lymphocytes in vitro, has previously been demonstrated to possess antigenic determinants coded by genes in the I region of the H-2 gene complex of the mouse. The studies presented here provide evidence that allogeneic effect factor also possesses antigenic determinants identical or cross-reactive with beta2-microglobulin. These observations suggest an important role for beta2-microglobulin in the mechanism of cell-cell interactions and the consequences of such interactions on lymphocyte triggering and differentiation.