Rabbit Immune System Research Articles

Effect of selection for growth rate on the rabbit (Oryctolagus cuniculus) immune system and its response after experimental Staphylococcus aureus infection.

The aim of the work was to evaluate if genetic selection for daily gain may affect the immune system. Two experiments were performed. The first one involved 80 rabbit females and their first two litters to explore the effect of selection on the ability of animals to maintain immune competence. Two generations from a line selected for average daily gain (ADG) were evaluated (VR19 generation 19th, n = 43; VR37 generation 37th, n = 37). In females, the effect of selection and its interaction with physiological state were not significant for any trait. In litters, the selection criterion increased the granulocyte to lymphocyte ratio. The second experiment involved 73 19-week-old females (VR19, n = 39; VR37, n = 34) to explore the effect of genetic selection on immune response after S. aureus infection. The VR37 rabbit females had lower counts for total lymphocytes, CD5+, CD4+, CD8+, CD25+, monocytes, the CD4+/CD8+ ratio and platelets than those of VR19 (-14, -21, -25, -15, -33, -18, -11 and -11%, respectively; P < 0.05). VR37 had less erythema (-8.4 percentage points; P < 0.05), fewer nodules (-6.5 percentage points; P < 0.05) and a smaller nodule size (-0.65 cm3 on 7day post-inoculation; P < 0.05) compared to VR19. Our study suggests that genetic selection for average daily gain does not negatively affect the maintenance of a competent immune system or the ability to establish immune response. It seems that such selection may improve the response to S. aureus infections.

Heat Stress Affects Faecal Microbial and Metabolic Alterations of Rabbits.

Heat stress can impair the rabbit immune system, induce oxidative stress, and cause many complications. These diseases are characterized by metabolic disorders, but the underlying mechanism is unknown. As a result, the current research determines the effects of HS on intestinal microorganisms in rabbits and the metabolic pathway disorders caused by HS. Twelve rabbits were randomly assigned to one of two groups: CON (22–24°C) and HS (30°C–32°C). Both the groups were treated for 15 days. Blood and fecal samples were collected on day 15. Serum immune oxidation indices were determined using a commercial ELISA kit, and the microbiome of rabbit feces was studied using 16S rRNA gene sequencing. Non-targeted metabolomics was analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPC MS/MS). The findings revealed that HS significantly increased IgG and T-AOC levels in serum, whereas it decreased TNF-α and IL-10. NMDS analysis revealed a substantial difference in bacterial community composition between HS and CON groups. At the phylum level, the abundance of Firmicutes, Protobacteria, and Verrucomicrobiota was significantly higher in the HS group, whereas the abundance of Bacteriodota was reduced in the CON group. V9D2013 group, Haloplasma, Comamonas, Clostridium sensu stricto 1, Ruminiclostridium, Syntrophus Lutispora, at the genus level Syntrophorhabdus, Paeniclostridium, Clostridium sensu stricto 6, Candidatus Caldatribacterium, Spirochaeta Synergistaceae, Syner-01, [Eubacterium] xylanophilum group, Cellulosilyticum, ADurb.Bin120, and Devosia were significantly upregulated in the HS group. The metabolism of the HS group was considerably upregulated compared with the metabolism of the CON group, according to principal component analysis (PCA) and least-squares discriminant analysis (PLS-DA). HS increased the concentrations of 4-pyridoxic acid, kynurenine, 20-OH-leukotriene B4, and dopamine and decreased the concentration of pyridoxal. In the rabbit gut, these compounds primarily impact the metabolic pathways of vitamin B6, tryptophan, neutrophil activation, and prolactin. 4-Pyridoxic acid, pyridoxal, kynurenine, 20-OH-leukotriene B4, and dopamine are essential inflammatory response markers and oxidative stress.

Tumor Infiltrating Lymphocytes in Pet Rabbit Mammary Carcinomas: A Study with Relevance to Comparative Pathology.

Simple SummaryThe interaction between tumors and immune cells influences tumor fate, i.e., regression, growth, or even metastases. The evaluation of tumor infiltrating lymphocytes (TILs) in human breast cancer has prognostic value. Pet rabbits develop spontaneous mammary carcinomas and have an immune system that is comparable with that of humans, so that they have the potential to provide an animal model for human breast cancer. To further substantiate this similarity, this study examined TILs in 107 pet rabbit mammary carcinomas according to criteria established for human breast cancer. For TIL evaluation routinely stained microscopic sections were examined by light microscopy. Relevant histological and immunohistochemical tumor characteristics were obtained from a data base. Results showed that increased presence of stromal TILs was statistically associated with histological tumor features indicative of a less aggressive biological behavior, i.e., reduced tumor cell proliferation and a lower histological grade. The expression by tumor cells of calponin, a presumed tumor suppressor protein, was also associated with their reduced proliferation and a higher percentage of stromal TILs. Data suggest that higher percentages of stromal TILs may have the potential to serve as favorable prognostic indicator in rabbit mammary carcinomas and support the value of pet rabbits for comparative research.Tumor infiltrating lymphocytes (TILs) serve as prognostic biomarker in human breast cancer. Rabbits have the potential to act as animal model for human breast cancer, and close similarities exist between the rabbit and human immune system. The aim of this study is to characterize TILs in pet rabbit mammary carcinomas and to statistically correlate results with histological and immunohistochemical tumor characteristics. Microscopic evaluation of TILs was performed in hematoxylin and eosin stained sections of 107 rabbit mammary carcinomas according to international guidelines for human breast cancer. Data on histological features of malignancy, estrogen and progesterone receptor status and calponin expression were obtained from the data base. This study revealed a statistical association between stromal TILs in the central tumor (CT) and infiltrative margin. Higher maximal percentages of stromal TILs at the CT were statistically correlated with decreased mitotic count and lower tumor grade. An increased number of calponin positive tumor cells was statistically associated with a lower mitotic count and a higher percentage of stromal TILs. Results suggest that higher percentages of stromal TILs are useful biomarkers that may point toward a favorable prognosis in rabbit mammary carcinomas and support the concept of the use of rabbits for translational research.

Genetic Diversity of IGHM and IGHE in the Leporids Revealed Different Patterns of Diversity in the Two European Rabbit Subspecies (O. cuniculus algirus and O. c. cuniculus).

Simple SummaryThe study of European rabbit immunoglobulin genes has contributed decisively to the current knowledge on antibody structure and diversification. The European rabbit has also been increasingly used as an animal model for the study of many human diseases, such as syphilis, tuberculosis, and AIDS. As such, the study of its immune system genes is of crucial relevance, but the study of rabbit immunoglobulins has focused only on the IgG and IgA antibodies. In this study, we added to the knowledge of the rabbit immune system by investigating the genetic diversity of two antibodies, IgM and IgE, in wild and domestic rabbits as well as other rabbit close species. With the data obtained in this study, we showed a high similarity between the different rabbit close species studied and we pointed out important genetic differences in the wild and domestic rabbits. Our findings are a valuable tool for the management of rabbit wild populations and domestic breeds and may contribute to the identification of immunoglobulins genetic variants with greater efficiency against pathogens.The European rabbit (Oryctolagus cuniculus) has been an important model for immunological studies but the study of its immunoglobulins (Ig) has been restricted to its unique IgA and IgG. Here, we studied the genetic diversity of IgM and IgE in several species of leporids and performed population genetics studies on European rabbit wild populations and domestic breeds. The leporids sequencing showed that these Ig are well conserved (98% sequence similarity among leporids), For IgM the Cµ1 and Cµ4 were the most diverse and most conserved domains, respectively, while for IgE the Cε1 was the most diverse domain and Cε2 and Cε3 the most conserved domains. The differences in the pattern of most conserved and most diverse domain between the Ig isotypes are most likely related to each isotype function. The genetic population data showed contrasting results for IgM and IgE. For both Ig, as expected, a greater diversity was observed in the original species range, the Iberian Peninsula. However, unexpectedly the genetic diversity found for IgE in the domestic animals is higher than that for the French wild populations. These results will increase knowledge of the genetic diversity of leporids and wild and domestic rabbit populations and are important tools for the management of wild populations and rabbitries.

Chia (Salvia hispanica) harvest residue induces cytokine expression in rabbits

The seed of chia plant (Salvia hispanica) is characterized by a high content of polyunsaturated fatty acids, which is an important source of -linolenic acid for human and animal consumption. During the harvest of the seed, waste is generated that contains remnants of leaves, stems and some seeds, which is generally discarded. The objective of the present work was to evaluate the eect of chia seed residue (CSR) on protein expression of the rabbit immune system, when added as a supplement in the diets of animals deliberately induced to an intestinal infection. Twenty rabbits (New Zealand x California) were randomly distributed in five treatments and fed fieve diets with different percentages of CSR inclusion (0, 10, 20, 30 and 40%). Quantification of the relative expression of the anti-inflammatory Interleukin-10 (IL-10) and Tumor Necrosis Factor (TNF-α) genes showed that as CSR inclusion levels increased up to 40%, mRNA expression of IL-10 increased significantly (22.4-fold) with respect to the control, while TNF- mRNA expression was inversely proportional, where a signicant increase (7.47-fold) in mRNA expression was found in the control group. It is concluded that the indirect inclusion of α-linolenic acid through the consumption of CSR induces a positive response in the immune system of the rabbits and represents an alternative for the formulation of rations with nutraceutical effects.

Effects of Oregano (Origanum vulgare L.) and Rosemary (Rosmarinus officinalis L.) Aqueous Extracts On in vitro Rabbit Immune Responses

In order to investigate the effects of some dietary phytoderivates (Origanum vulgare L. and Rosmarinus officinalis L.) on rabbit immune system, 100 New Zealand mixed-sex rabbits weaned at 30 days of age were split into homogeneous groups submitted to the following dietary treatments: 1) Standard diet (C); 2) C +150 ppm Vit E (E); 3) C +0.2% oregano (O); 4) C +0.2% rosemary (R) and 5) C +0.1% oregano + 0.1% rosemary (OR). Blood samples were drawn from rabbits at 30 and 90 days of age (ten rabbits/diet group at Time 0 and 1, respectively) to investigate the blood lymphocyte subset evolution, the in vitrolymphocyte proliferation (in presence or absence of mitogens) responses and the Immunoglobulin M(IgM) concentration in the supernatants of lymphocyte cultures. A diet effect was observed in the O and OR groups, where the lymphocytes proliferation responses to pokeweed mitogen (PWM; ***P<0.001, in the O group) or the interleukin-2 production (IL-2; ***P<0.001, for both groups) at Time 1 were significantly higher. The IgM levels were systematically higher in the O, OR and E cells culture supernatants (**P<0.01). Age did not affect the rabbit lymphocyte subset evolution nor the in vitrolymphocyte proliferation. Data obtained in the present study show that rabbit’s dietary supplementation with oregano elicits positive effects on the adaptive immune response.

An overview of the lagomorph immune system and its genetic diversity.

Our knowledge of the lagomorph immune system remains largely based upon studies of the European rabbit (Oryctolagus cuniculus), a major model for studies of immunology. Two important and devastating viral diseases, rabbit hemorrhagic disease and myxomatosis, are affecting European rabbit populations. In this context, we discuss the genetic diversity of the European rabbit immune system and extend to available information about other lagomorphs. Regarding innate immunity, we review the most recent advances in identifying interleukins, chemokines and chemokine receptors, Toll-like receptors, antiviral proteins (RIG-I and Trim5), and the genes encoding fucosyltransferases that are utilized by rabbit hemorrhagic disease virus as a portal for invading host respiratory and gut epithelial cells. Evolutionary studies showed that several genes of innate immunity are evolving by strong natural selection. Studies of the leporid CCR5 gene revealed a very dramatic change unique in mammals at the second extracellular loop of CCR5 resulting from a gene conversion event with the paralogous CCR2. For the adaptive immune system, we review genetic diversity at the loci encoding antibody variable and constant regions, the major histocompatibility complex (RLA) and T cells. Studies of IGHV and IGKC genes expressed in leporids are two of the few examples of trans-species polymorphism observed outside of the major histocompatibility complex. In addition, we review some endogenous viruses of lagomorph genomes, the importance of the European rabbit as a model for human disease studies, and the anticipated role of next-generation sequencing in extending knowledge of lagomorph immune systems and their evolution.

Rabbit anti-HIV-1 monoclonal antibodies raised by immunization can mimic the antigen-binding modes of antibodies derived from HIV-1-infected humans.

The rabbit is a commonly used animal model in studying antibody responses in HIV/AIDS vaccine development. However, no rabbit monoclonal antibodies (MAbs) have been developed previously to study the epitope-specific antibody responses against HIV-1 envelope (Env) glycoproteins, and little is known about how the rabbit immune system can mimic the human immune system in eliciting such antibodies. Here we present structural analyses of two rabbit MAbs, R56 and R20, against the third variable region (V3) of HIV-1 gp120. R56 recognizes the well-studied immunogenic region in the V3 crown, while R20 targets a less-studied region at the C terminus of V3. By comparison of the Fab/epitope complex structures of these two antibodies raised by immunization with that of the corresponding human antibodies derived from patients chronically infected with HIV-1, we found that rabbit antibodies can recognize immunogenic regions of gp120 and mimic the binding modes of human antibodies. This result can provide new insight into the use of the rabbit as an animal model in AIDS vaccine development.

In vivo studies on the immunotoxic effects of microcystins on rabbit

Microcystins (MCs) are the toxic molecules produced by common cyanobacterium in freshwater blooms. Their toxicities raise severe health issues in livestock and human beings. In current study, the immunotoxic effects of MC-LR were investigated in rabbit through evaluating the dynamics of white blood cell (WBC) numbers and cytokine production such as interleukin-3 (IL-3), IL-4, IL-6, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α). MCs at the high dose (50 μg MC-LReq kg(-1) ) significantly induced increase in the WBC number but decrease in the Th1 (IFN-γ, TNF-α) and Th2 (IL-3, IL-4, IL-6) production. In the low dose group(12.5 μg MC-LReq kg(-1) ), the number of WBC and the production of IFN-γ, IFN-α, IL-4, IL-3, and IL-6 increased gradually in first 12 h, reach the peaks at 12 h, and dropped after 24 h. Significantly positive correlations were found between the cytokines production of IL-4 and IL-6, IFN-γ and IFN-α, or IL-4 and IFN-γ. In conclusion, MC-LR is able to disturb the rabbit immune system and there exists time-dose response relationship in the MC-LR-eliciting perturbation, which probably give a better insight into investigating the immunotoxicity mechanisms of MCs in vivo. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.

Expression and localization of rabbit B-cell activating factor (BAFF) and its specific receptor BR3 in cells and tissues of the rabbit immune system

Rabbits are widely used for vaccine development, and investigations of human infectious and autoimmune diseases such as Systemic Lupus Erythematosus (SLE). For these applications, we cloned, sequenced and expressed rabbit B-cell Activating Factor (BAFF), and localized BAFF in cells and tissues of the rabbit immune system. The rabbit homolog of the human BAFF binding site (miniBR3 peptide) within the BAFF-specific receptor BR3 was synthesized. This 26-residue core domain binds to recombinant rabbit BAFF protein. Flow cytometric analyses using purified recombinant rabbit BAFF combined with real-time PCR findings revealed that BAFF detected on peripheral blood B-cells from normal rabbits is probably complexed to BAFF receptors rather than produced by the B-cells. BAFF was detected in developing appendix of young rabbits by immunohistochemical staining suggesting that BAFF plays a role during the period following birth when rabbit B-cell development and pre-immune antibody repertoire diversification and selection is occurring.

Detection of positive selection in the major capsid protein VP60 of the rabbit haemorrhagic disease virus (RHDV)

Mutations were analysed in the major capsid protein VP60 of the rabbit haemorrhagic disease virus (RHDV), a calicivirus responsible for high mortality rates in both wild and domestic European rabbits (Oryctolagus cuniculus). Likelihood of positive selection was estimated using the PAML software applied to 43 non-identical complete sequences of the major capsid protein. Three codons showed signs of positive selection (with posterior probabilities over 95%), one of them is located in the region containing the major antigenic determinants (region E). The presence of positively selected codons (PSCs) in other regions may suggest the existence of other antigenic regions on the major capsid protein that stimulate protective immune responses. At all the 3 PSCs, variation contributes to putative N-glycosylation sites of the protein. An N-glycosylation site is deleted in the non-pathogenic strain RCV. Some of the substitutions at PSCs may alter the polarity and the charge of the protein with possible implications in the protein structure and host interaction. The detection of PSCs should allow a better understanding of the interaction between RHDV and the rabbit immune system.

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host

Myxoma virus (MV) is a poxvirus that evolved in Sylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts.

Acquired immune dysfunction in rabbits experimentally infected with an infectious molecular clone of the bovine immunodeficiency virus (BIV127).

To investigate the effect of bovine immunodeficiency virus (BIV) infection on the rabbit immune system, we studied the proliferative responses of peripheral blood lymphocytes (PBLs) of rabbits experimentally inoculated with BIV. All BIV127-inoculated rabbits seroconverted after 6 weeks and remained seropositive over a prolonged period of time. Assays for specific lymphocyte reactivity to concanavalin A (Con A) were performed monthly for over 1 year. One-hundred percent of infected rabbits developed abnormally low T cell responses, as measured by Con A stimulation. By 3 months postinoculation, the PBL response to Con A was diminished and remained depressed for 6 months. All animals were clinically asymptomatic within 14 months of BIV inoculation. By 15 and 16 months postinoculation, two of three infected rabbits exhibited recurrent lowering of the T cell responsiveness including a decrease in absolute PBL counts. One of these animals died unexpectedly. Our results further confirmed that a functional impairment of lymphocytes was induced early in the course of BIV infection, prior to clinical disease. These findings suggested that BIV infection may mimic asymptomatic infection of human immunodeficiency virus (HIV) and provided further evidence of the importance of BIV-induced disease in rabbits as a relevant model for the study of AIDS.

N-terminal ten amino acid sequence determined for B-cell differentiation factor derived from rabbit breast milk cell supernatant.

The rabbit has provided a useful model for the study of mucosal immunity (1). Indeed, the bulk of the rabbit immune system lies within the gut associated lymphoid tissue. At birth, these tissues are poorly developed; however, shortly after birth, these gut associated lymphoid tissues enlarge and become capable of mounting an immune response (2). Temporally, these changes occur during breast feeding. Breast milk contains a variety of cellular elements, including T cells and B cells, as well as a predominance of macrophages, all capable of responding to polyclonal activation and antigen (3). This study defines the N-terminal 1–10 AA sequence for a naturally occurring B-cell differentiation factor arising from rabbit breast milk cells.

The rabbit immune system: cells regulating the proliferative response of purified T cells to concanavalin A and phytohaemagglutinin.

T cell specific, B cell specific and Ia specific polyclonal antisera, as well as monoclonal antibodies, were employed to characterize cells involved in regulation of T cells, proliferating upon stimulation with concanavalin A or phytohaemagglutinin. Evidence for Ia+ accessory cells was obtained and the constellation of membrane antigens was determined by cytotoxic cell kill with the above mentioned antibodies. Help given by Ia+ cells was not blocked by polyclonal antibody against Ia, in the absence of complement. There was indirect evidence that a fraction of helper/accessory cells were Ia-.

In vitro studies of the rabbit immune system. VIII. The production of rabbit T cell growth factor (TCGF) and its relationship to mouse and human TCGF

Rabbit spleen cells (1 X 10(6)/ml) stimulated with Con A (2.5 micrograms/ml) begin producing T cell growth factor (TCGF) activity within 2-3 h at 37 degrees C and reach a plateau after 20-24 h. Lymphocytes from the mesenteric lymph nodes (MLN) also produce TCGF activity but require higher lectin and/or cell concentrations for optimal production. TCGF generation by MLN can be improved by including a small proportion of spleen cells (10-40%). Rabbit lymphocytes also produce TCGF in serum-free, protein-free medium, but the Con A concentration must be reduced to 0.5-1.25 micrograms/ml. Rabbit TCGF activity eluted from gel filtration columns at a volume equivalent to approximately 15,000 molecular weight, similar to human TCGF activity. However, when rabbit, mouse and human TCGFs were compared for their ability to support proliferation by activated cells from the 3 species, rabbit and mouse TCGFs appeared more similar. In all cases, the homologous combinations of cells and TCGF were most efficient. Human TCGF would support some proliferative activity in all 3 cell types but rabbit and mouse TCGFs failed to support the growth of human cells.

In vitro studies of the rabbit immune system. IX. Extended culture of rabbit cytotoxic cells and the generation of TCGF-dependent T lymphocyte lines

Rabbit T lymphocytes with cytotoxic activity for mouse target cells can be maintained in culture for several weeks by periodically restimulating with fresh mouse cells or by culturing with a source of TCGF. The former procedure greatly enriches the cultured cells for cytotoxic activity but has the disadvantage of introducing cellular debris. Cell growth and cytotoxic activity waned after 4-6 weeks using either procedure. However, T lymphocyte lines (TLL) could be isolated from limiting dilution cultures containing mitomycin C-treated mouse 'feeder' cells and a source of TCGF. These cells grew out with a frequency of one in 50-150 and approximately 15% of these growing cells had cytotoxic activity. Some cytotoxic cells lost their lytic activity after 4-5 months but others have persisted for over 7 months. Some TLL have now been growing for over 20 months.

In vitro studies of the rabbit immune system. VII. The generation of rabbit anti-mouse cytotoxic T lymphocytes

Lymphocytes from normal or immunized rabbits generated cell-mediated cytotoxic activity (CML) after culture with mitomycin C-treated mouse stimulator cells for 4–7 days. CML activity was detected in short term (4–6 h) isotope-release assays using 51Cr-labeled tumor cells or mitogen stimulated blast cells as targets. Rabbit CML effectors could distinguish between different mouse strains including congenics differing only at H-2. It was previously shown that rabbit CML precursors and effectors expressed antigens recognized by a specific anti-T cell serum (ATS). The current results demonstrated that T-enriched fractions from nylon wool columns were enriched for CTL precursors and were sufficient to generate CML responses. These data were most consistent with the xenogeneic CML being mediated by rabbit cytotoxic T lymphocytes (CTL) analogous to murine CTL. Rabbit lymphocytes also produced a strong mixed lymphocyte (MLC) response when tested in microculture with mouse stimulator cells. However, optimal CML and MLC responses did not occur in lymphocytes from the same organ sources or subpopulations. These data implied that CML activity could be generated with little, if any, proliferation necessary.

The rabbit immune system: characterization of cell surface markers and functional properties of rabbit lymphocytes

V. Introduction Contributions of different lymphocyte populations to immune responses A. Induction of antibody formation B. Antigen induced lymphocyte proliferation C. Cytotoxic lymphocytes D. Mitogenic responses E. Suppressor cells F. Effect of thymectomy G. Role of macrophages Surface IgG class and allotype expression A. Immunoglobulin class expression B. The passive uptake problem C. Immunoglobulin allotype expression T Cells and surface immunoglobulin expression A. Mitogen response overlap B. Marker overlap Summary and conclusion

The inhibition of susceptible and hypersensitive reactions by protein-lipopolysaccharide complexes from phytopathogenic pseudomonads: relationship to polysaccharide antigenic determinants

Protein-lipopolysaccharide (pr-LPS) complexes were purified from a virulent strain of Pseudomonas tabaci (NCPPB 1427) and two incompatible strains ( P. aptata NCPPB 2664 and P. lachrymans NCPPB 1436). They all contained two major polypeptides with mol. wts of 20 000 and 40 000. Slide agglutination tests with O- or pr-LPS-antisera produced against antigens from P. aptata NCPPB 2664 showed that the surface antigens of P. aptata had common determinants with P. tabaci NCPPB 1427, but not with P. lachrymans NCPPB 1436. Precipitin ring tests of heat-stable antigens (121 °C) in the presence of pr-LPS antiserum indicated that most determinants were carried by lipopolysaccharides. Pr-LPS complexes from the three strains, pre-injected into tobacco leaves, prevented hypersensitive confluent necrosis evoked by seven incompatible pseudomonads, and delayed or inhibited the development of the susceptible reaction induced by five compatible strains. These effects were unrelated to the degree of virulence of compatible strains and to the type of surface antigenic determinants of the whole bacterium, as recognized by the rabbit immune system. This suggests a common mechanism of interaction in the protected tissue, causing plant tolerance to various degrees towards different strains. Pr-LPS complexes of P. tabaci NCPPB 1427 were most effective in inducing protection, consistent with the possibility that compatible strains may produce surface substances having higher tolerance-inducing activity.