Burgdorferi-specific Antibodies Research Articles

Seroprevalence, seroconversion and seroreversion of Borrelia burgdorferi-specific IgG antibodies in two population-based studies in children and adolescents, Germany, 2003 to 2006 and 2014 to 2017.

BackgroundLyme borreliosis (LB), caused by Borrelia burgdorferi (Bb), is the most common tick-borne infection in Germany. Antibodies against Bb are prevalent in the general population but information on temporal changes of prevalence and estimates of seroconversion (seroincidence) and seroreversion are lacking, especially for children and adolescents.AimWe aimed at assessing antibodies against Bb and factors associated with seropositivity in children and adolescents in Germany.MethodsWe estimated seroprevalence via two consecutive cross-sectional surveys (2003-2006 and 2014-2017). Based on a longitudinal survey component, we estimated annual seroconversion/seroreversion rates.ResultsSeroprevalence was 4.4% (95% confidence interval (CI): 3.9-4.9%) from 2003 to 2006 and 4.1% (95% CI: 3.2-5.1%) from 2014 to 2017. Seroprevalence increased with age, was higher in male children, the south-eastern regions of Germany and among those with a high socioeconomic status. The annual seroconversion rate was 0.3% and the annual seroreversion rate 3.9%. Males were more likely to seroconvert compared with females. Low antibody levels were the main predictor of seroreversion.ConclusionWe did not detect a change in seroprevalence in children and adolescents in Germany over a period of 11 years. Potential long-term changes, for example due to climatic changes, need to be assessed in consecutive serosurveys. Seroconversion was more likely among children and adolescents than among adults, representing a target group for preventive measures. Seroreversion rates are over twice as high in children and adolescents compared with previous studies among adults. Thus, seroprevalence estimates and seroconversion rates in children are likely underestimated.

Dynamics of Borrelia burgdorferi-Specific Antibodies: Seroconversion and Seroreversion between Two Population-Based, Cross-Sectional Surveys among Adults in Germany.

Lyme borreliosis (LB) caused by Borrelia burgdorferi spp. is the most common human tick-borne disease in Europe. Although seroprevalence studies are conducted in several countries, rates of seroconversion and seroreversion are lacking, and they are essential to determine the risk of infection. Seropositivity was determined using a two-step approach—first, a serological screening assay, and in the event of a positive or equivocal result, a confirmatory immunoblot assay. Seroconversion and seroreversion rates were assessed from blood samples taken from participants included in two nation-wide population-based surveys. Moreover, the impact of antigen reactivity on seroreversion rates was assessed. The seroprevalence of antibodies reacting against B. burgdorferi spp. in the German population was 8.5% (95% CI 7.5–9.6) in 1997–99 and 9.3% (95% CI 8.3–10.4) in 2008–2011. Seroprevalence increased with age, up to 20% among 70–79 year-olds. The age-standardized seroprevalence remained the same. The yearly seroconversion rate was 0.45% (95% CI: 0.37–0.54), and the yearly seroreversion rate was 1.47% (95% CI: 1.24–2.17). Lower levels of antibodies were associated with seroreversion. Participants with a strong response against antigen p83 had the lowest odds on seroreversion. Given the yearly seroreversion rate of 1.47% and a seroprevalence up to 20% in the oldest age groups, at least 20% of the German population becomes infected with B. burgdorferi in their lifetime. The slight increase in seroprevalence between the two serosurveys was caused by an aging population.

ELISPOT assays and their diagnostic potential in Lyme disease and Lyme neuroborreliosis.

ELISPOT assays and their diagnostic potential in Lyme disease and Lyme neuroborreliosis.

Development of a sensitive PCR-dot blot assay to supplement serological tests for diagnosing Lyme disease

Laboratory diagnosis of Lyme disease is difficult and presently dependent on detecting Borrelia burgdorferi-specific antibodies in patient serum with the disadvantage that the immune response to B. burgdorferi can be weak or variable, or alternatively, the slow and inefficient culture confirmation of B. burgdorferi. PCR tests have previously shown poor sensitivity and are not routinely used for diagnosis. We developed a sensitive and specific Lyme Multiplex PCR-dot blot assay (LM-PCR assay) applicable to blood and urine samples to supplement western blot (WB) serological tests for detecting B. burgdorferi infection. The LM-PCR assay utilizes specific DNA hybridization to purify B. burgdorferi DNA followed by PCR amplification of flagellin and OspA gene fragments and their detection by southern dot blots. Results of the assay on 107 and 402 clinical samples from patients with suspected Lyme disease from Houston, Texas or received at the IGeneX laboratory in Palo Alto, California, respectively, were analyzed together with WB findings. The LM-PCR assay was highly specific for B. burgdorferi. In the Texas samples, 23 (21.5%) patients antibody-negative in WB assays by current US Centers for Disease Control (CDC) recommended criteria were positive by LM-PCR performed on urine, serum or whole blood samples. With IGeneX samples, of the 402 LM-PCR positive blood samples, only 70 met the CDC criteria for positive WBs, while 236 met IGeneX criteria for positive WB. Use of the LM-PCR assay and optimization of current CDC serological criteria can improve the diagnosis of Lyme disease.

Ability of an oral formulation of afoxolaner to protect dogs from Borrelia burgdorferi infection transmitted by wild Ixodes scapularis ticks.

A randomized, blinded, negative controlled study was conducted to determine whether treatment with afoxolaner (NexGard®, Merial, Inc.) would prevent the transmission of Borrelia burgdorferi to dogs by wild caught Ixodes scapularis ticks. Twenty healthy dogs were randomly assigned to two groups of ten dogs each. Ten dogs were treated orally on Day 0 at a dose near the minimum recommended dose of afoxolaner of 2.5mg/kg (actual doses 2.5-3.1mg/kg) and ten control dogs were not treated. On Day 28, each dog was infested with approximately 50 adult unfed wild caught I. scapularis that had a 67% B. burgdorferi infection rate (determined by polymerase chain reaction). On Day 33, live ticks were counted and removed. No ticks were found on treated dogs while control dogs had an average of 21.4 ticks. To detect infection, the B. burgdorferi-specific C6 antibody SNAP® 4Dx® test (IDEXX) was performed on serum collected before infestation (all dogs seronegative on Days -6 and 27) and on Days 48, 63, 77 and 92. The ten treated dogs remained seronegative through the end of the study (Day 92), while nine out of the ten control dogs were infected, as demonstrated by their seroconversion to being positive for the presence of the B. burgdorferi-specific C6 antibody starting on Day 48. In this study, all dogs treated with NexGard® 28days prior to challenge with wild caught I. scapularis ticks were protected from B. burgdorferi infection, while nine out of the ten untreated control dogs were infected.

Acute Hemiparesis Revealing Neuroborreliosis in a 3-Year-Old Boy

Case Study: We report a previously healthy 3-year-old boy who presented with acute left hemiparesis without signs of ongoing infection. MRI lacked signs of vascular abnormalities but instead demonstrated a restriction in the diffusion-weighted imaging of the right lobulus paracentralis with a corresponding leptomeningeal contrast enhancement. Suspecting a case of focal meningoencephalitis empirical antibiotic and antiviral treatment was initiated, however, lumbar puncture revealed sterile cerebrospinal fluid (CSF) without abnormalities in cell count, glucose, or total protein content. A tick bite was reported 1 month before presentation without any local erythematous skin lesion. Accordingly, laboratory results showed intrathecal production of quantitative (IgM/IgG pos) as well as qualitative Borrelia burgdorferi-specific antibodies in liquor and serum (IgM > 86 U/mL, IgG 39 U/mL) indicating that a CNS infection with Borrelia burgdorferi was imminent. Thus, antiviral therapy was stopped and ceftriaxone treatment was continued for 14 days. The hemiparesis disappeared within a few hours and the boy recovered without any neurologic sequelae. MRI findings were negative for either a preceding epileptic seizure or a migraine attack and EEG was normal, so Todd paresis is unlikely. In conclusion, our findings indicate that our patient suffered from a Borrelia-associated meningoencephalitis which presented itself with an acute unilateral paresis, which regressed within hours. We conclude that neuroborreliosis should be considered as a differential diagnosis in children with stroke-like episode, even without elevated cell count or total protein in CSF.

Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection

The etiologic agent of Lyme disease, Borrelia burgdorferi, localizes preferentially in the extracellular matrix during persistence. In chronically infected laboratory mice, there is a direct association between B. burgdorferi and the proteoglycan decorin, which suggests that decorin has a role in defining protective niches for persistent spirochetes. In this study, the tissue colocalization of B. burgdorferi with decorin and the dynamics of borrelial decorin tropism were evaluated during chronic infection. Spirochetes were found to colocalize absolutely with decorin, but not collagen I in chronically infected immunocompetent C3H mice. Passive immunization of infected C3H-scid mice with B. burgdorferi-specific immune serum resulted in the localization of spirochetes in decorin-rich microenvironments, with clearance of spirochetes from decorin-poor microenvironments. In passively immunized C3H-scid mice, tissue spirochete burdens were initially reduced, but increased over time as the B. burgdorferi-specific antibody levels waned. Concurrent repopulation of the previously cleared decorin-poor microenvironments was observed with the rising tissue spirochete burden and declining antibody titer. These findings indicate that the specificity of B. burgdorferi tissue localization during chronic infection is determined by decorin, driven by the borrelia-specific antibody response, and fluctuates with the antibody response.

CXCL13 may improve diagnosis in early neuroborreliosis with atypical laboratory findings

BackgroundCurrent guidelines regarding Lyme neuroborreliosis [LNB] require the presence of intrathecal Borrelia burgdorferi-specific antibody production for the definite diagnosis of LNB. However, about 20% of early stage infections present without an elevated antibody index. Moreover, intrathecal B. burgdorferi specific antibody synthesis may persist long after successful therapy of LNB. Recently published data indicate that CXCL13 seems to be a promising diagnostic tool for early stage LNB. In addition, CXCL13 might be suitable for treatment monitoring.Case presentationWe report on a 39-year-old male patient from southern Germany, who has been suffering from subfebrile body temperatures and meningeal headache for six weeks. On the second day after hospital admission he developed peripheral palsy of the VII. cranial nerve. Cerebrospinal fluid (CSF) analysis showed granulocytic pleocytosis, elevated total protein and blood-CSF barrier dysfunction. Differential diagnostics for granulocytic pleocytosis were unremarkable. Only a second lumbar puncture, on day 6 after admission, revealed a lymphocytic pleocytosis. Serologic testing pointed to clear intrathecal Borrelia specific IgG antibody production. Interestingly, no anti-OspC antibodies were detectable. DNA of the rare Borrelia garinii OspA-type 7 could be amplified from the first CSF sample. The monitoring of CXCL13 in all CSF samples documented a fast decrease from 5000 pg/ml to 450 pg/ml after appropriate antibiotic treatment.ConclusionCXCL13 is a novel biomarker with high sensitivity and specificity for acute LNB. Our data show, that CXCL13 might be helpful in unclear cases and support the presumption that it might be a valuable tool for treatment monitoring. Anti-OspC antibody negativity is a rare observation, given the need of OspC for infection of the human hosts. Most likely this is due to a lack of sensitivity of OspC immunoblots that are unable to detect rare OspC variants.

Acute neuroborreliosis with involvement of the central nervous system

Background Lyme neuroborreliosis has not been previously reported in Taiwan. The purpose of this study was to describe the important characteristics of Lyme neuroborreliosis caused by Borrelia burgdorferi-like species in Taiwanese patients. Methods Patients with acute neurological symptoms without a clear explanation during September 2005 to December 2008 were enrolled. All patients received extensive auxiliary investigations, including clinical evaluation by neurological examination, electrophysiological and neuroimaging studies, serological screening tests of serum and cerebrospinal fluid (CSF) by indirect immunofluorescent assay, and Western immunoblot analysis conducted for seroreactivities in serum and CSF of Borrelia burgdorferi-specific IgM and IgG antibodies. Results Eleven patients who presented with acute central nervous system (CNS) syndrome fulfilled the diagnostic criteria for neuroborreliosis. In the CSF studies, lymphocytic pleocytosis with elevation of total protein and normal glucose was noted in 9 patients. The clinical syndromes were confirmed by magnetic resonance imaging and electrophysiological studies. Ten of 11 patients were found to have brain stem or spinal cord lesions on neuroimaging studies, and 8 patients had concomitant peripheral nervous system involvement with electrophysiological evidence of multiple root lesions with an acute or subacute course. Conclusions Lyme neuroborreliosis presenting as acute CNS syndrome with peripheral nervous system involvement simultaneously in the disease course, especially acute myelopolyradiculitis, in Taiwan is different from Lyme neuroborreliosis seen in Europe and North America. The treatment outcome is variable and based on the severity of initial neurological deficits, early diagnosis, and early management.

One-Year Duration of Immunity Induced by Vaccination with a Canine Lyme Disease Bacterin

Laboratory-reared beagles were vaccinated with a placebo or a bacterin comprised of Borrelia burgdorferi S-1-10 and ospA-negative/ospB-negative B. burgdorferi 50772 and challenged after 1 year with B. burgdorferi-infected Ixodes scapularis ticks. For the placebo recipients, spirochetes were recovered from 9 (60%) skin biopsy specimens collected after 1 month, and the organisms persisted in the skin thereafter. Ten (67%) dogs also developed joint infection (3 dogs), lameness or synovitis (7 dogs), or B. burgdorferi-specific antibodies (8 dogs). For the vaccine recipients, spirochetes were recovered from 6 (40%) skin biopsy specimens collected after 1 month. However, subsequent biopsy specimens were negative, and the dogs failed to develop joint infection (P = 0.224), lameness/synovitis (P = 0.006), or Lyme disease-specific antibody responses (P = 0.002). The bacterin provided a high level of protection for 1 year after immunization, and the addition of the OspC-producing B. burgdorferi 50772 provided enhanced protection.

The Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates

Borrelia burgdorferi, the agent of Lyme disease, is transmitted by ticks. During transmission from the tick to the host, spirochetes are delivered with tick saliva, which contains the salivary protein Salp15. Salp15 has been shown to protect spirochetes against B. burgdorferi-specific antibodies. We now show that Salp15 from both Ixodes ricinus and Ixodes scapularis protects serum-sensitive isolates of Borrelia burgdorferi sensu lato against complement-mediated killing. I. ricinus Salp15 showed strong protective effects compared to those of I. scapularis Salp15. Deposition of terminal C5b to C9 (one molecule each of C5b, C6, C7, and C8 and one or more molecules of C9) complement complexes, part of the membrane attack complex, on the surface of B. burgdorferi was inhibited in the presence of Salp15. In the presence of normal human serum, serum-sensitive Borrelia burgdorferi requires protection against complement-mediated killing, which is provided, at least in part, by the binding to the tick salivary protein Salp15.

Mice Lacking CD21 and CD35 Proteins Mount Effective Immune Responses againstBorrelia burgdorferiInfection

CD21/35(-/-) mice, deficient in CD21 and CD35 (complement receptors 2 and 1, respectively), were infected with Borrelia burgdorferi to assess the role of these receptors in a chronic bacterial infection. Although CD21/35(-/-) mice on both C57BL/6 and BALB/c backgrounds produced less B. burgdorferi-specific antibodies than did wild-type mice, spirochete levels and arthritis severity were similar.

Detection of Immune Complexes Is Not Independent of Detection of Antibodies in Lyme Disease Patients and Does Not Confirm Active Infection with Borrelia burgdorferi

The Borrelia burgdorferi-specific immune complex (IC) test, which uses polyethylene glycol (PEG) precipitation to isolate ICs from serum, has been used as a research test in the laboratory diagnosis of early Lyme disease (LD) and has been proposed as a marker of active infection. We examined whether B. burgdorferi-specific antibodies were present within PEG-precipitated ICs (PEG-ICs) in patients with LD, posttreatment Lyme disease syndrome, and controls, including individuals who received the outer surface protein A (OspA) vaccine. Using a B. burgdorferi whole-cell enzyme-linked immunosorbent assay (ELISA), we obtained positive PEG-IC results not only in patients with a history of LD, but also in individuals vaccinated with OspA vaccine. The frequency of positive PEG-IC ELISAs in OspA vaccinees was significantly higher with ELISA-reactive than with ELISA-negative unprocessed serum samples (P=0.001), demonstrating dependency between the tests. Similar results were found using samples from rhesus macaques infected with B. burgdorferi, uninfected macaques vaccinated with OspA, and controls. Therefore, testing for the presence of antibodies against B. burgdorferi in PEG-IC preparations is not more likely to reflect active infection than testing in unprocessed serum and should not be used in individuals who received the OspA vaccine.

Myeloid differentiation antigen 88 deficiency impairs pathogen clearance but does not alter inflammation in Borrelia burgdorferi-infected mice.

The spirochete Borrelia burgdorferi causes acute inflammation in mice that resolves with the development of pathogen-specific adaptive immunity. B. burgdorferi lipoproteins activate innate immune cells via Toll-like receptor 2 (TLR2), but TLR2-deficient mice are not resistant to B. burgdorferi-induced disease, suggesting the involvement of other TLRs or non-TLR mechanisms in the induction of acute inflammation. For this study, we used mice that were deficient in the intracellular adapter molecule myeloid differentiation antigen 88 (MyD88), which is required for all TLR-induced inflammatory responses, to determine whether the interruption of this pathway would alter B. burgdorferi-induced disease. Infected MyD88(-/-) mice developed carditis and arthritis, similar to the disease in wild-type (WT) mice analyzed at its peak (days 14 and 28) and during regression (day 45). MyD88(-/-) macrophages produced tumor necrosis factor alpha only when spirochetes were opsonized, suggesting a role for B. burgdorferi-specific antibody in disease expression. MyD88(-/-) mice produced stronger pathogen-specific Th2-dependent immunoglobulin G1 (IgG1) responses than did WT mice, and their IgM titers remained significantly elevated through 90 days of infection. Despite specific antibodies, the pathogen burden was 250-fold higher in MyD88(-/-) mice than in WT mice 45 days after infection; by 90 days of infection, the pathogen burden had diminished substantially in MyD88(-/-) mice, but it was still elevated compared to that in WT mice. The elevated pathogen burden may be explained in part by the finding that MyD88(-/-) peritoneal macrophages could ingest spirochetes but degraded them more slowly than WT macrophages. Our results show that MyD88-dependent signaling pathways are not required for B. burgdorferi-induced inflammation but are necessary for the efficient control of the pathogen burden by phagocytes.

First culture isolation of Borrelia lonestari, putative agent of southern tick-associated rash illness.

Southern tick-associated rash illness (STARI) is a Lyme disease-like infection described in patients in the southeastern and south-central United States, where classic Lyme disease is relatively rare. STARI develops following the bite of a lone star tick (Amblyomma americanum) and is thought to be caused by infection with an "uncultivable" spirochete tentatively named Borrelia lonestari. In this study, wild lone star ticks collected from an area where B. lonestari is endemic were cocultured in an established embryonic tick cell line (ISE6). The cultures were examined by dark-field microscopy for evidence of infection, and spirochete identity and morphology were evaluated by flagellin B and 16S rRNA gene sequence, by reaction to Borrelia-wide and B. burgdorferi-specific monoclonal antibodies, and by electron microscopy. Live spirochetes were first visualized in primary culture of A. americanum ticks by dark-field microscopy 14 days after the cell culture was inoculated. The sequences of the flagellin B and 16S rRNA genes of cultured spirochetes were consistent with previously reported sequences of B. lonestari. The cultured spirochetes reacted with a Borrelia-wide flagellin antibody, but did not react with an OspA antibody specific to B. burgdorferi, by indirect fluorescent antibody testing. Electron microscopy demonstrated organisms that were free and associated with ISE6 cells, with characteristic Borrelia sp. morphology. This study describes the first successful isolation of B. lonestari in culture, providing a much needed source of organisms for the development of diagnostic assays and forming a basis for future studies investigating the role of the organism as a human disease agent.

Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis.

Cyclooxygenase (Cox) is a key enzyme in the biosynthetic metabolism of prostaglandins. The inducible isoform of Cox-2 has been implicated in inflammation and its specific inhibition can be used to treat noninfectious inflammatory diseases, such as rheumatoid arthritis. Borrelia burgdorferi, the agent of Lyme disease, can induce joint inflammation. Here we show that B. burgdorferi induced the upregulation of cox-2 gene expression in murine joints at the onset of arthritis in infected mice. The level of mRNA expression correlated with the degree of inflammation. The specific inhibition of Cox-2 diminished the degree of joint inflammation, without affecting B. burgdorferi-specific antibody or cytokine responses. Cox-2 activity is therefore associated with the genesis of infectious arthritis caused by B. burgdorferi.

Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis

Cyclooxygenase (Cox) is a key enzyme in the biosynthetic metabolism of prostaglandins. The inducible isoform of Cox-2 has been implicated in inflammation and its specific inhibition can be used to treat noninfectious inflammatory diseases, such as rheumatoid arthritis. Borrelia burgdorferi, the agent of Lyme disease, can induce joint inflammation. Here we show that B. burgdorferi induced the upregulation of cox-2 gene expression in murine joints at the onset of arthritis in infected mice. The level of mRNA expression correlated with the degree of inflammation. The specific inhibition of Cox-2 diminished the degree of joint inflammation, without affecting B. burgdorferi-specific antibody or cytokine responses. Cox-2 activity is therefore associated with the genesis of infectious arthritis caused by B. burgdorferi.

Borrelia burgdorferi-specific monoclonal antibodies derived from mice primed with Lyme disease spirochete-infected Ixodes scapularis ticks.

We have generated a panel of IgG monoclonal antibodies (MAbs) directed against Borrelia burgdorferi strain B31 antigens, using a method whereby mice were primed with organisms naturally inoculated by Ixodes scapularis nymphal ticks. Western blot analysis showed that these MAbs recognized several B. burgdorferi B31 antigens, including the complement inhibitor factor H-binding proteins ErpA/I/N and ErpC. Two other MAbs were specific for the RevA protein, and have enabled characterization of that previously unknown protein. The data presented here suggest that the production of MAbs from animals infected by tick-bite is a potentially useful tool for the identification of novel proteins synthesized by B. burgdorferi during mammalian infection.

Role of osteopontin in murine Lyme arthritis and host defense against Borrelia burgdorferi.

Several genetic loci in the mouse have been identified that regulate the severity of Lyme arthritis. The region of chromosome 5 including the osteopontin (OPN) gene (Opn) has been identified in intercross populations of C3H/HeN x C57BL/6 and C3H/HeJ x BALB/cAnN mice. OPN is of particular interest as it is involved in the maintenance and remodeling of tissue during inflammation, it regulates production of interleukin-10 (IL-10) and IL-12 (cytokines implicated in Lyme arthritis), it is necessary for host control of certain bacterial infections, and mice displaying different severities of Lyme arthritis possess different alleles of the OPN gene. Macrophages and splenocytes from OPN-deficient mice on mixed C57BL/6J-129S or inbred 129S backgrounds were stimulated with the Pam(3)Cys modified lipoprotein from Borrelia burgdorferi, OspA. OPN was not required for OspA-induced cytokine production; however, macrophages from 129S-Opn(-/-) mice displayed a reduced level of IL-10 production. OPN was also not required for resistance to severe arthritis, as B. burgdorferi-infected 129S-Opn(-/-) mice developed mild arthritis, as did their wild-type littermates. Arthritis was more severe in OPN-deficient mice on the mixed C57BL/6J-129S backgrounds than in inbred mice of either strain. This increase was most likely due to a gene(s) closely linked to Opn on chromosome 5 in conjunction with other randomly assorting genes. Deficiency in OPN did not influence the numbers of spirochetes in tissues from B. burgdorferi-infected mice, indicating OPN is not part of the host defense to this pathogen. Interestingly, there was no alteration in the B. burgdorferi-specific antibody isotypes in OPN-deficient mice, indicating that its effect on helper T-cell responses is not relevant to the host response to B. burgdorferi.

CD4+ T helper 1 cells facilitate regression of murine Lyme carditis.

Murine Lyme borreliosis, caused by infection with the spirochete Borrelia burgdorferi, results in acute arthritis and carditis that regress as a result of B. burgdorferi-specific immune responses. B. burgdorferi-specific antibodies can attenuate arthritis in mice deficient in both B cells and T cells but have no effect on carditis. Because macrophages comprise the principal immune cell in carditis, T-cell responses that augment cell-mediated immunity may be important for carditis regression. To investigate this hypothesis, we examined the course of Lyme carditis in mice selectively deficient in B cells or alphabeta T cells. Our results show that carditis regresses in B-cell-deficient B10.A(k) mice but not in alphabeta T-cell-deficient mice, independently of the mouse strain background. Despite prominent macrophage infiltrates, hearts from B. burgdorferi-infected alphabeta T-cell-deficient mice had less mRNA for tumor necrosis factor alpha as measured by reverse transcription-PCR compared to infected control mice. Anti-inflammatory cytokine mRNA levels were equivalent. Adoptive transfer of gamma interferon-secreting CD4+ T cells into infected alphabeta T-cell-deficient mice promoted carditis resolution. These results show that alphabeta T cells can promote resolution of murine Lyme carditis and are the first demonstration of a beneficial role for CD4+ T helper 1 cells in this disease.