Transfer of osteosarcoma-specific cell-mediated immunity in hamsters by rabbit dialyzable leukocyte extracts

We have investigated the transfer of specific cell-mediated immunity (CMI) to osteosarcoma-associated antigens (OSAA) to hamsters with dialyzable leukocyte extracts (DLE) from OSAA-immunized rabbits. The transfer of specific CMI was determined by leukocyte adherence inhibition (LAI) assay and skin testing. DLE was prepared from rabbits immunized with OSAA, purified protein derivative (PPD), or fibrosarcoma cell plasma membrane preparation (FSM). Control DLE was prepared from rabbits injected with 0.85% NaCl. Significant leukocyte adherence inhibition was observed with leukocytes from hamsters that had received OSAA-specific, PPD-specific, and FSM-specific rabbit DLE, when OSAA, PPD, and FSM were used as antigens, respectively. Similarly, significant ear swelling after injection of OSAA, PPD, or FSM was observed only in hamsters that had received DLE from rabbits immunized with OSAA, PPD, or FSM, respectively. These results suggest that CMI specific for OSAA, PPD, or FSM can be transferred to normal hamsters by DLE from immunized rabbits.     

Relationships between cell-mediated immunity and the IgE antibody response: I. Lymphotoxin production to DNP-Ascaris conjugates

The purpose of this paper is to present evidence for the suitability of a lymphotoxin (LT) assay as an in vitro correlate of cell-mediated immunity (CMI) to a hapten-carrier conjugate known to stimulate a high IgE antibody response. This would be used in a study of the factors influencing the relationship(s) between CMI and IgE antibody responses to the same antigen. Antigen-induced LT was assayed on actinomycin-inhibited, chromium-51-labeled L929 fibroblasts, using supernatants obtained from spleen and lymph node cells of animals immunized with 2,4-dinitrophenyl-Ascaris conjugates. Although LT was present at all times tested, beginning at Day 10, its concentration varied with time after immunization, adjuvant used, and cell type assayed. The induction of LT was T-cell dependent and conjugate specific. LT was produced by nonadherent cells. Adherent cells from immunized animals produced L-cell cytotoxin in the absence of antigen stimulation when tested before Day 10.     

Protection of rhesus monkeys against infection with minimally pathogenic simian-human immunodeficiency virus: correlations with neutralizing antibodies and cytotoxic T cells

We studied the capacity of active immunization of rhesus monkeys with HIV-1 envelope protein (Env) to induce primary virus cross-reactive neutralizing antibodies to prevent infection following intravenous challenge with simian-human immunodeficiency virus (SHIV). Monkeys were immunized with the human immunodeficiency type 1 (HIV-1) strain R2 Env. Initially, the Env was expressed in vivo by an alphavirus replicon particle system, and then it was administered as soluble oligomeric gp140. Concurrently, groups of monkeys received expression vectors that encoded either simian immunodeficiency virus (SIV) gag/pol genes or no SIV genes in vivo to test the additional protective benefit of concurrent induction of virus-specific cell-mediated immune (CMI) responses. Groups of control monkeys received either the gag/pol regimen or sham immunizations. The antibodies induced by the Env immunization regimen neutralized diverse primary HIV-1 strains. Similarly, potent CMI responses were induced by the gag/pol regimen, as measured by gamma interferon enzyme-linked immunospot assays. Differences in the responses among groups of monkeys strongly suggested that there was interference between the Env and gag/pol immunization regimens. Complete protection of some of the monkeys against infection after intravenous challenge with the partially pathogenic SHIV(DH12R (Clone 7)) was associated independently with both neutralizing antibody and CMI responses. Protection was associated with SHIV(DH12 (Clone 7)) serum neutralizing antibody titers of > or =1:80 or with cellular immune responses corresponding to >2,000 spot forming cells per 10(6) peripheral blood mononuclear cells. Immunization was also associated with a reduction in the magnitude and duration of virus load. Induction of cross-reactive, primary HIV-1-neutralizing antibodies is feasible and, when potent, may result in complete protection against infection with a heterologous challenge virus strain.     

Studies of delayed hypersensitivity to L. Monocytogenes in mice: nature of cells involved in passive transfers

C3Hf/Umc mice were immunized by an intravenous injection of a sublethal dose of live Listeria monocytogenes. The animals developed delayed-type hypersensitivity (DH) concomitant with infectious immunity to this organism. Delayed hypersensitivity could be transferred to normal lethally irradiated mice with spleen cells from immune animals. The immune cells cells responsible for transfer of adoptive immunity were susceptible to in vitro cytolytic action of anti-theta iso-antibody and complement, since such treatment rendered these cells incapable of further passive transfer of specific immunity to Listeria. The acquired DH to Listeria persisted in mice after 900 R lethal irradiation, provided normal syngeneic bone marrow cells were also administered, thus indicating the persistance of a cell population in the immune irradiated mice, resistant to effects of radiation. The radio resistant nature of this immune cell population was further demonstrated by passive transfer with spleen cells, derived from preimmunized lethally irradiated mice to normal syngeneic mice or to lethally irradiated nonimmunized hosts reconstituted with normal bone marrow which then responded to antigenic challenge with DH.Treatment of the immune radio resistant spleen cells in vitro with anti-theta and complement eliminated passive transfers of DH by these cells; however, this effect was less obvious than similar treatment of the immune, nonirradiated, spleen cells.     

Immunity to carcinogen-induced transplantable fibrosarcoma in B2B2 chickens: V. Relationship to tumor cell-specific delayed hypersensitivity and serum antibody

Lasting immunity to the chemically induced (DMBA) fibrosarcomas (CHCT-NYU1, 2, and 4) of SC chickens ($\text{B2}\text{B2}$) can be obtained by injection of Corynebacterium parvum (CP)-primed chickens with tumor cells and CP in one wing and tumor cells alone in the other wing. The local delayed hypersensitivity (DH) reaction to CP in the wing inhibits local growth completely, whereas the tumor on the contralateral side shows transient growth. In the present studies, the development of tumor immunity was studied in detail by monitoring DH and antibody formation to the tumor cells and adoptive immunity with spleen cells in Winn tests. Injection of NYU1 cells alone in normal or CP-treated animals induced transient immunity in Winn tests in 50% of the animals, weak DH reactivity, and antibody detectable by immunofluorescence within the first 2 weeks. Chickens receiving both NYU1 cells and CP in one wing and NYU1 cells alone on the other side developed stronger DH reactions to the tumor cells and a higher incidence of immunity in Winn tests which was sustained throughout the period of observation. Antibody levels were similar to those of animals receiving tumor cells alone. In contrast, injection of CP and tumor cells on one side without a tumor challenge on the contralateral side did not induce detectable immunity in CP-primed chickens. Chickens immunized to NYU2 and 4 cells were also tested for DH reactivity and antibody formation. Studies on the cross-reactivity between the tumor lines showed that there was cross-reactivity at the humoral level while at the cellular level this was not apparent. However, animals immune to one tumor line rejected transplants of another tumor line. Observations on the antibody specificity(s) suggested that it was not directed against minor histocompatibility or avian sarcoma viral antigens. SC embryo fibroblasts could induce DH, and serum antibody induced by tumor cells usually reacted also with such embryo cells.     

Trypanosoma rhodesiense: variant specificity of immunity induced by irradiated parasites.

Rats immunized with irradiated Trypanosoma rhodesiense resisted infection with the homologous strain. When similarly immunized rats were challenged with parasites obtained from rhesus monkeys infected with the same strain, resistance depended on when parasites were obtained from the donor monkeys. Immunized rats challenged with trypanosomes obtained from a monkey during the first peak of parasitemia were solidly immune; immunized rats challenged with trypanosomes obtained from monkeys after their initial peak of parasitemia all succumbed to the challenging infection. These observations indicate that parasites of a variant antigenic specificity arose during the course of the monkey infections. Neutralization tests performed on the various isolates from rats and monkeys using antiserum obtained from immunized rats confirmed that the immunity produced by irradiated trypanosomes was variant specific.     

Depo-Provera abrogates attenuated lentivirus-induced protection in male rhesus macaques challenged intravenously with pathogenic SIVmac239

BACKGROUND: Progesterone administration prior to intravaginal challenge with pathogenic SIVmac239 decreases the protective efficacy of live attenuated vaccines in rhesus macaques. METHODS: To determine if progesterone alters the efficacy of live attenuated vaccines through local or systemic effects, seven male rhesus macaques were immunized with SHIV89.6 and then challenged intravenously with SIVmac239. Three of these animals were treated with Depo-Provera 30 days prior to the SIV challenge. RESULTS: The SHIV animals had significantly lower plasma viral RNA levels than the unimmunized control monkeys, but the Depo-Provera treated, SHIV-immunized animals did not. Despite the lack of protection, the Depo-Provera SHIV animals had strong SIV specific T-cell responses. However, altered patterns of NK frequency and CD38 T-cell expression prior to SIV challenge were observed in Depo-Provera SHIV animals. CONCLUSIONS: Depo-Provera eliminates live-attenuated lentivirus vaccine efficacy in male rhesus monkeys through systemic effects on antiviral immunity and/or viral replication.     

Protective immunity induced by porin in experimental mouse salmonellosis

The induction of protective immunity to mouse salmonellosis by porin from Salmonella typhimurium LT2 was studied. The immunization with porin induced a high level of protective immunity to salmonellosis in BALB/c mice. Mice immunized with porin exhibited significant levels of delayed-type hypersensitivity response and interleukin-2 production, indicating that porin was capable of inducing cell-mediated immunity (CMI). Furthermore, we found that both T cells and sera taken from the porin-immunized mice could transfer the protection against salmonellosis into nonimmunized mice. These observations suggested that a high level of the protection to salmonellosis obtained by the porin immunization resulted from the induction of CMI in addition to humoral immunity.     

Longitudinal cellular immune responses in asymptomatic and symptomatic Brugia malayi-infected Indian leaf monkey Presbytis entellus

To investigate the cell-mediated immune (CMI) responses of the host during the development of acute filarial disease manifestations, we studied the sequential changes in CD4+ and CD8+ T-cell subsets, leukocyte migration inhibition (LMI) response to Brugia malayi adult worm antigen, and concanavalin-A (ConA) and filarial antigen-induced lymphocyte transformation (LT) in the Indian leaf monkey (Presbytis entellus)-B. malayi model. Filarial infection was established in monkeys by subcutaneous inoculations of infective larvae (L3) (700-1,250 L3/monkey) in multiple doses, and the infected monkeys were categorized as symptomatic (Sym) and asymptomatic (Asym) depending on whether or not acute clinical manifestations were shown by them. In Sym monkeys, LMI response to homologous adult parasite antigen was significantly suppressed as compared to Asym monkeys. In Asym monkeys, LMI response varied among the animals; 2 showed an increase throughout the study period and 2 showed suppression at different time points. When compared with Asym monkeys, CD8+ T cells in Sym monkeys showed a trend of significant increase after day 180 postinoculation (PI). CD4+ T cells remained within the normal range till day 300 (PI), after which they showed a marginal increase. ConA-stimulated LT was suppressed in Asym monkeys from day 60 PI. Antigen-stimulated LT was unresponsive in both Asym and Sym animals. Thus, the host's LT response to ConA is suppressed in Asym animals, and alteration in CD8+ T-cell number and LMI response in Sym monkeys may be involved in the development of the acute disease manifestations in this model.     

The regulation of lymphotoxin release from stimulated human lymphocyte cultures: the requirement for continual mitogen stimulation

Concanavalin A (Con A) activates nonimmune human lymphocytes in vitro to undergo transformation, DNA synthesis, and lymphotoxin (LT) secretion. LT secretion is inhibited (within minutes) when free and membrane-bound Con A are removed by washing or incubation with the competitive inhibitor, α-methyl mannoside. LT secretion can be reinitiated by addition of fresh Con A. While LT can be rapidly regulated, blast transformation and cellular DNA synthesis are under less restrictive control. Although they appear to be related, LT secretion and lymphocyte transformation seem to be regulated by independent control mechanisms. These studies indicate that recognition and contact of lymphocyte membrane sites initiate as well as regulate the efferent or destructive phase of cell-mediated immune (CMI) reactions. A model of how lymphocytes could employ LT in specific and nonspecific cytodestructive CMI reactions is presented.     

Genetic influences on behavioral inhibition and anxiety in juvenile rhesus macaques

In humans and other animals, behavioral responses to threatening stimuli are an important component of temperament. Among children, extreme behavioral inhibition elicited by novel situations or strangers predicts the subsequent development of anxiety disorders and depression. Genetic differences among children are known to affect risk of developing behavioral inhibition and anxiety, but a more detailed understanding of genetic influences on susceptibility is needed. Nonhuman primates provide valuable models for studying the mechanisms underlying human behavior. Individual differences in threat-induced behavioral inhibition (freezing behavior) in young rhesus monkeys are stable over time and reflect individual levels of anxiety. This study used the well-established human intruder paradigm to elicit threat-induced freezing behavior and other behavioral responses in 285 young pedigreed rhesus monkeys. We examined the overall influence of quantitative genetic variation and tested the specific effect of the serotonin transporter promoter repeat polymorphism. Quantitative genetic analyses indicated that the residual heritability of freezing duration (behavioral inhibition) is h ² = 0.384 ( P  = 0.012) and of 'orienting to the intruder' (vigilance) is h ² = 0.908 ( P  = 0.00001). Duration of locomotion and hostility and frequency of cooing were not significantly heritable. The serotonin transporter polymorphism showed no significant effect on either freezing or orienting to the intruder. Our results suggest that this species could be used for detailed studies of genetic mechanisms influencing extreme behavioral inhibition, including the identification of specific genes that are involved in predisposing individuals to such behavior.     

Antibody Responses to a Novel Plasmodium falciparum Merozoite Surface Protein Vaccine Correlate with Protection against Experimental Malaria Infection in Aotus Monkeys

The Block 2 region of the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum has been identified as a target of protective immunity by a combination of seroepidemiology and parasite population genetics. Immunogenicity studies in small animals and Aotus monkeys were used to determine the efficacy of recombinant antigens derived from this region of MSP-1 as a potential vaccine antigen. Aotus lemurinus griseimembra monkeys were immunized three times with a recombinant antigen derived from the Block 2 region of MSP-1 of the monkey-adapted challenge strain, FVO of Plasmodium falciparum, using an adjuvant suitable for use in humans. Immunofluorescent antibody assays (IFA) against erythrocytes infected with P. falciparum using sera from the immunized monkeys showed that the MSP-1 Block 2 antigen induced significant antibody responses to whole malaria parasites. MSP-1 Block 2 antigen-specific enzyme-linked immunosorbent assays (ELISA) showed no significant differences in antibody titers between immunized animals. Immunized animals were challenged with the virulent P. falciparum FVO isolate and monitored for 21 days. Two out of four immunized animals were able to control their parasitaemia during the follow-up period, whereas two out of two controls developed fulminating parasitemia. Parasite-specific serum antibody titers measured by IFA were four-fold higher in protected animals than in unprotected animals. In addition, peptide-based epitope mapping of serum antibodies from immunized Aotus showed distinct differences in epitope specificities between protected and unprotected animals.     

Induction of primary and inhibition of secondary antibody response to hapten by hapten conjugates of type III pneumococcal polysaccharide.

Tri- or dinitrophenylated pneumococcal polysaccharide type III (TNP- or DNP SIII)) induced a primary 19S anti-TNP response without generating immunological memory to the hapten in LAF₁ mice. Hapten-hemocyanin (TNP-KLH) or hapten conjugates of B. abortus organisms (DNP-BA) induced both 19S and 7S primary responses and memory to the hapten. Spleen cells from mice immunized with TNP-KLH or DNP-BA did not give adoptive memory responses upon challenge with hapten-SIII and, in fact, were inhibited from responding to their homologous hapten conjugates by simultaneous injection of hapten-SIII. Incubation of TNP-KLH-primed spleen cells for as short as 5 min at 0 °C with 10 μg of TNP-SIII per milliliter virtually abolished their ability to give 19S and 7S memory responses to TNP-KLH upon transfer into irradiated recipients. It is suggested that a difference in avidity and/or number of anti-TNP receptors per cell between virgin and primed B cells may be an important factor in determining whether the cells will be stimulated or inhibited by exposure to hapten-SIII. Another factor may be a difference between virgin and memory cells in their requirement for T-cell help.     

In vivo assessment of tumor-induced nonspecific suppression of contact sensitivity

Summary Normal BALB/c mice were assessed for 2,4-dinitrofluorobenzene (DNFB)-induced contact sensitivity following adoptive transfer of macrophages (Mo). T cells, or their derived products, from normal or tumor-bearing hosts (TBH). Contact sensitivity (CS) was measured by a quantitative radioisotopic ear assay, a total in vivo system based on localization of IP-injected iodinated human serum albumin ([¹²⁵I]HSA) in the DNFB-challenged ear. Adoptive transfer of low or high doses of TBH T cells or their derived supernatants into normal recipients suppresed their responsiveness, while Mo supernatants enhanced it. Moreover, in all cases adoptive transfer of TBH cells or supernatants resulted in a lower CS response than did their normal counterparts. These results further corroborate our previous in vitro data indicating that T cells, or Mo and T cell soluble products, possess immunoregulatory capabilities in vivo.Abbreviations DNFB 2,4-dinitrofluorobenzene - TBH tumor-bearing host - Mo macrophages - ¹²⁵I-HSA iodinated-human serum albumin - CMI cell-mediated immunity - CS contact sensitivity; Ig, immunoglobulin - C complement     

Cell-mediated immunity to mouse adenovirus infection. Macrophage migration inhibition test.

Cell-mediated immunity (CMI) to mouse adenovirus (M-Ad) infection was studied by macrophage migration inhibition test (MMI) as one of in vitro correlates of CMI. Both direct and indirect tests showed clearly that migration of packed peritoneal exudate cells (PEC) (immune mouse or nonimmune guinea pig) was remarkably inhibited; MIF was produced by interactions between immune PEC and infected cell extracts and between immune spleen cells and infected cells or their extracts. The antigen(s) responsible for the above MMI was demonstrated in 6- to 12-hour infected ME cells, and FUdR-treated infected ME cells. Since under these conditions there is S antigen(s) synthesis but not capsid antigen synthesis, the antigen(s) concerned must be an S antigen(s). T cells sensitized to infected cells were shown to be required to induce MMI. The MMI is specific for M-Ad, since no cross MMI was observed between M-Ad and SV40 systems. Time course study of the development of CMI to M-Ad by MMI tests showed that CMI became detectable 4 days post-infection (pi), reached its peak level about 10 days pi, and faded away rapidly in about 10 days thereafter.     

Studies of the mechanisms for the induction of in vivo tumor immunity. I. Induction of primary and secondary cell-mediated cytotoxic responses by adoptive transfer of lymphocytes.

Cell-mediated immunity to FBL-3, a syngeneic Friend virus-induced leukemia in C57BL/6 mice, could be adoptively transferred. Characteristic primary and secondary cytotoxic responses could be induced by adoptive transfer of normal and presensitized lymphocytes, respectively. In vivo tumor immunity could also be produced by adoptive transfer of presensitized lymphocytes. Both the primary and secondary cell-mediated cytotoxic reactions were T-cell dependent. The specificity of these reactions was primarily directed against F (Friend) type-specific antigen and FMR (Friend, Moloney, Rauscher) common antigen. The cytotoxic responses produced by adoptive transfer experiments gave better correlation to in vivo tumor immunity than those generated by in vitro mixed lymphocyte tumor cell culture reactions.     

CD4+ T cells acting independently of antibody contribute to protective immunity to Plasmodium chabaudi infection after apical membrane antigen 1 immunization

Apical membrane Ag 1 (AMA1) is a leading malaria vaccine candidate. Homologues of AMA1 can induce protection in mice and monkeys, but the mechanism of immunity is not understood. Mice immunized with a refolded, recombinant, Plasmodium chabaudi AMA1 fragment (AMA1B) can withstand subsequent challenge with P. chabaudi adami. Here we show that CD4+ T cell depletion, but not gammadelta T cell depletion, can cause a significant drop in antiparasite immunity in either immunized normal or immunized B cell KO mice. In normal mice, this loss of immunity is not accompanied by a decline in Ab levels. These observations indicate a role for AMA1-specific Ab-independent T cell-mediated immunity. However, the loss of immunity in normal CD4+ T cell-depleted mice is temporary. Furthermore, immunized B cell KO mice cannot survive infection, demonstrating the absolute importance of B cells, and presumably Ab, in AMA1-induced immunity. CD4+ T cells specific for a cryptic conserved epitope on AMA1 can adoptively transfer protection to athymic (nu/nu) mice, the level of which is enhanced by cotransfer of rabbit anti-AMA1-specific antisera. Recipients of rabbit antisera alone do not survive. Some protected recipients of T cells plus antisera do not develop their own AMA 1-specific Ab response, suggesting that AMA 1-specific CMI alone can protect mice. These data are the first to demonstrate the specificity of any protective CMI response in malaria and have important implications for developing a malaria vaccine.     

A partially attenuated simian immunodeficiency virus induces host immunity that correlates with resistance to pathogenic virus challenge.

Three infectious, attenuated molecular clones of simian immunodeficiency virus (SIVmac) were tested for viral and host determinants of protective immunity. The viruses differed in degree of virulence from highly attenuated to moderately attenuated to partially attenuated. Levels of immune stimulation and antiviral immunity were measured in rhesus macaques inoculated 2 years previously with these viruses. Monkeys infected with the highly attenuated or moderately attenuated viruses had minimal lymphoid hyperplasia, normal CD4/CD8 ratios, low levels of SIV-specific antibodies, and cytotoxic T-lymphocyte activity against p55gag (Gag) or gp160env (Env). Monkeys infected with the partially attenuated virus had moderate to marked lymphoid hyperplasia, normal CD4/CD8 ratios, high levels of SIV-specific antibodies, and cytotoxic T-lymphocyte activity against both Gag and Env. After pathogenic virus challenge, monkeys immunized with the partially attenuated virus had 100- to 1,000-fold-lower viral load in peripheral blood mononuclear cells and lymph node mononuclear cells than naive control animals. One of four monkeys immunized with the highly attenuated virus and two of four monkeys immunized with the moderately attenuated virus developed similarly low viral loads after challenge. These three attenuated strains of SIV induced a spectrum of antiviral immunity that was inversely associated with their degree of attenuation. Only the least attenuated virus induced resistance to challenge infection in all immunized monkeys.     

Cell-mediated immunity following experimental vaccinations with Candida albicans ribosomes

The aim of the present study was to ascertain whether cell-mediated immunity (CMI) is induced in animals by vaccination with Candida albicans ribosomes. Delayed type hypersensitivity (DTH) was detected in vivo in ribosome-vaccinated mice and guinea pigs by the footpad swelling and skin tests, respectively. The observed DTH was similar to that induced by live C. albicans organisms. A lymphocyte transformation assay was used for in vitro detection of CMI. The tritiated thymidine incorporation assays revealed that spleen lymphocytes from mice immunized with C. albicans ribosomes were stimulated by the ribosomal antigen. The findings establish that C. albicans ribosomes are able to induce CMI in experimental animals.     

125I-fibrin deposition in contact sensitivity reactions in the mouse. Sensitivity of the assay for quantitating reactions after active or passive sensitization

We investigated the clotting associated with delayed hypersensitivity (DH) responses in the mouse by sensitizing the animals to the contactant oxazolone (Ox), and then administering 125I-guinea pig fibrinogen i.v. 10 to 30 min before antigen challenge 5 days later. Early (4 to 8 hr) contact sensitivity (CS) responses in immunized mice were barely detectable by three conventional measures of CS, but the total 125I-cpm in ears challenged with hapten was 3.6 to 4.5 X that in control ears challenged with vehicle alone; moreover, the amount of urea-insoluble cpm (cross-linked 125I-fibrin-associated cpm) in the reactions to Ox was 6.5-fold to 8.2-fold that present in the control reactions. In 24 hr reactions that were near peak intensity by measurements of ear swelling, ear weight ratios, and ratios of 125I-5-iodo-2-deoxyuridine-labeled leukocyte infiltration, the cpm in antigen-challenged ears exceeded that in control ears by 13-fold to 53-fold. In addition, antigen-challenged ears contained 27 to 300 X the urea-insoluble cpm present in control ears. 125I-Fibrin deposition was not a specific characteristic of CS reactions, because a small amount of urea-insoluble reactivity was also detected in some reactions to Ox in native mice. Nevertheless, the assay was exquisitely sensitive and readily detected quantitative differences between the immunologically specific and nonspecific reactions at very early intervals after challenge or with suboptimal doses of antigen. Furthermore, it was more sensitive than conventional tests of CS in detecting the reactions elicited in mice that had been passively sensitized to Ox by adoptive transfer of immune lymph node cells. Finally, we showed that the assay gave similar results when we tested CS reactions elicited in mast cell deficient WBB6F1-W/Wv and littermate normal (+/+) mice, demonstrating yet another similarity in the phenotype of DH reactions elicited in the presence or absence of mast cells.