Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK‐cell subset distribution in children

Human cytomegalovirus (HCMV) has been reported to reshape the NK‐cell receptor (NKR) distribution, promoting an expansion of CD94/NKG2C⁺ NK and T cells. The role of NK cells in congenital HCMV infection is ill‐defined. Here we studied the expression of NKR (i.e., NKG2C, NKG2A, LILRB1, CD161) and the frequency of the NKG2C gene deletion in children with past congenital infection, both symptomatic (n = 15) and asymptomatic (n = 11), including as controls children with postnatal infection (n = 11) and noninfected (n = 20). The expansion of NKG2C⁺ NK cells in HCMV‐infected individuals appeared particularly marked and was associated with an increased number of LILRB1⁺ NK cells in cases with symptomatic congenital infection. Increased numbers of NKG2C⁺, NKG2A⁺, and CD161⁺ T cells were also associated to HCMV infection. The NKG2C deletion frequency was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous NKG2C^+/+ genotype appeared associated with increased absolute numbers of NKG2C⁺ NK cells. Moreover, HCMV‐infected NKG2C^+/+ children displayed higher absolute numbers of NKG2A⁺ and total NK cells than NKG2C^+/? individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK‐cell compartment in children, revealing a modulatory influence of NKG2C copy number.     

Chronic Trichuris muris infection alters hematopoiesis and causes IFN‐γ‐expressing T‐cell accumulation in the mouse bone marrow

Proinflammatory cytokines produced during immune responses to infectious stimuli are well‐characterized to have secondary effects on the function of hematopoietic progenitor cells in the BM. However, these effects on the BM are poorly characterized during chronic infection with intestinal helminth parasites. In this study, we use the Trichuris muris model of infection and show that Th1 cell‐associated, but not acute Th2 cell‐associated, responses to chronic T. muris infection cause a major, transient expansion of CD48^?CD150^? multipotent progenitor cells in the BM that is dependent on the presence of adaptive immune cells and IFN‐γ signaling. Chronic T. muris infection also broadly stimulated proliferation of BM progenitor cells including CD48^?CD150⁺ hematopoietic stem cells. This shift in progenitor activity during chronic T. muris infection correlated with a functional increase in myeloid colony formation in vitro as well as neutrophilia in the BM and peripheral blood. In parallel, we observed an accumulation of CD4⁺, CD8⁺, and CD4^?CD8^? (double negative) T cells that expressed IFN‐γ, displaying activated and central memory‐type phenotypes in the bone marrow during chronic infection. Thus, these results demonstrate that Th1 cell‐driven responses in the intestine during chronic helminth infection potently influence upstream hematopoietic processes in the BM via IFN‐γ.     

Decrease in the Frequency of Circulating CD56+CD161+ NK Cells in Human Visceral Leishmaniasis

Background: Natural Killer (NK) cell plays an important role in the innate immune system and is known to produce IFN-γ at an early stage of infection that is essential to eliminate intracellular infection like Leishmania spp. It is already established that Leishmania parasite inhibits the activity of NK cells, avoiding the encounter with the early innate immune response. This, in turn, favors establishment and further dissemination of the infection. Methods: In the present study, we have tried to measure the frequency of different phenotypic subsets of NK cells among visceral leishmaniasis (VL) patients. Results: We have phenotyped three distinct three distinct subsets (CD56^–CD161⁺, CD56⁺CD161^–, and CD56⁺CD161⁺) of NK (CD3^–) cell using their specific markers CD161 and CD56. Conclusion: Interestingly, we observed selective loss of CD56⁺CD161⁺ subset of circulating NK (CD3^–) cells. Importantly, the other subsets (i.e., CD56^?CD161⁺ and CD56⁺CD161^–) of circulating NK cells remain unaffected as compared with healthy subjects.     

Human and mouse perforin are processed in part through cleavage by the lysosomal cysteine proteinase cathepsin L

Summary Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4⁺ T cells play a critical role in protective immunity, and that CD4⁺ T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4⁺ T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4⁺ T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post‐T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4⁺ T cells marked by down‐regulation of CD62L. These cells can be isolated from intestine‐draining mesenteric lymph nodes (MLN) from day 14 post‐infection, but are rare or absent in MLN before this and in spleen at all times post‐infection. Among CD4⁺ CD62L^low MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4⁺ CD62L^low T‐cell migration to the large intestinal mucosa is dependent on the family of Gα_i‐coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4⁺ CD62L^low cell migration to the large intestinal mucosa during T. muris infection.     

T regulatory cells and immune activation in Mycobacterium tuberculosis infection and the effect of preventive therapy

Mycobacterium tuberculosis (TB) often causes persistent infection and many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. We have studied dendritic cell (DC) subsets, regulatory T cells (Treg) and the expression of activation and apoptosis markers on CD4⁺ and CD8⁺ T cells in blood from patients with active TB (n = 20), subjects with positive QuantiFERON‐TB GOLD (QFT) test (LTBI, latent TB infection) (n = 20) before and after 3 months of preventive anti‐tuberculous therapy and from QFT‐negative controls (n = 28). The frequency of CD4⁺CD25⁺CD127^? Treg was highest in the group with active TB (P = 0.001), but also increased in the LTBI group (P = 0.006) compared to controls. The highest level of activated T cells, defined as CD38⁺HLA‐DR⁺ cells, was found in the active TB group, for the CD4⁺ T cell subset positively correlated to the level of CD25⁺CD127^? Treg (P < 0.001, r = 0.4268). After 3 months of preventive therapy, there was an increase in the fraction of foxp3⁺ Treg, but no differences in markers of activation or apoptosis. In conclusion, there seems to be an increased level of immune activation and Treg in both latent and active TB infection that is only modestly influenced by preventive therapy.     

Tracking antigen‐specific CD4+ T cells throughout the course of chronic Leishmania major infection in resistant mice

Primary Leishmania major infection typically produces cutaneous lesions that not only heal but also harbor persistent parasites. While the opposing roles of CD4⁺ T‐cell‐derived IFN‐γ and IL‐10 in promoting parasite killing and persistence have been well established, how these responses develop from naïve precursors has not been directly monitored throughout the course of infection. We used peptide:Major Histocompatibility Complex class II (pMHCII) tetramers to investigate the endogenous, parasite‐specific primary CD4⁺ T‐cell response to L. major in mice resistant to infection. Maximal frequencies of IFN‐γ⁺ CD4⁺ T cells were observed in the spleen and infected ears within a month after infection and were maintained into the chronic phase. In contrast, peak frequencies of IL‐10⁺ CD4⁺ T cells emerged within 2 weeks of infection, persisted into the chronic phase, and accumulated in the infected ears but not the spleen, via a process that depended on local antigen presentation. T helper type‐1 (Th1) cells, not Foxp3⁺ regulatory T cells, were the chief producers of IL‐10 and were not exhausted. Therefore, tracking antigen‐specific CD4⁺ T cells revealed that IL‐10 production by Th1 cells is not due to persistent T‐cell antigen receptor stimulation, but rather driven by early antigen encounter at the site of infection.     

Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to Toxoplasma gondii infection

Proteasome‐mediated proteolysis is responsible for the generation of immunogenic epitopes presented by MHC class I molecules, which activate antigen‐specific CD8⁺ T cells. Immunoproteasomes, defined by the presence of the three catalytic subunits LMP2, MECL‐1, and LMP7, have been hypothesized to optimize MHC class I antigen processing. In this study, we demonstrate that the infection of mice with a protozoan parasite, Toxoplasma gondii, induced the expression of LMP7 mRNA in APC and increased the capacity of APC to induce the production of IFN‐γ by antigen‐specific CD8⁺ T cells. In vitro infection of a DC cell line with T. gondii also induced the expression of LMP7 and resulted in enhanced proteasome proteolytic activity. Finally, mice lacking LMP7 were highly susceptible to infection with T. gondii and showed a reduced number of functional CD8⁺ T cells. These results demonstrate that proteasomes containing LMP7 play an indispensable role in the survival of mice infected with T. gondii, presumably due to the efficient generation of CTL epitopes required for the functional development of CD8⁺ T cells.     

Generation, specificity, and function of CD8+ T cells in Trypanosoma cruzi infection

Summary: CD8⁺ T cells are crucial to the control of Trypanosoma cruzi infection and probably act via multiple mechanisms, the most important being the production of interferon‐γ (IFN‐γ). In the absence of CD8⁺ T cells, mice quickly succumb to the infection or develop a more severe chronic disease. Reduced production of IFN‐γ by CD8⁺ T cells is also associated with increased severity of chagasic disease in humans. CD8⁺ T cells in chronic T. cruzi infection are maintained as effector memory cells, undergo rapid expansion, and demonstrate effector functions following re‐exposure to antigen. However, the initial generation of T. cruzi‐specific CD8⁺ T‐cell responses appears to be relatively slow to develop. In addition, the expression of the effector function of the CD8⁺ T cells is compromised in some tissues, particularly in muscle. The targets of effective CD8⁺ T‐cell responses in T. cruzi infection are multiple and varied, and they represent some of the best vaccine candidates described to date. Further analysis of CD8⁺ T cells will provide insight into the disease process in T. cruzi infection and should identify methods to assess and enhance immunity to T. cruzi infection and protection from the symptoms of Chagas' disease.     

Preferentially expanding Vγ1+ γδ T cells are associated with protective immunity against Plasmodium infection in mice

γδ T cells play a crucial role in controlling malaria parasites. Dendritic cell (DC) activation via CD40 ligand (CD40L)‐CD40 signaling by γδ T cells induces protective immunity against the blood‐stage Plasmodium berghei XAT (PbXAT) parasites in mice. However, it is unknown which γδ T‐cell subset has an effector role and is required to control the Plasmodium infection. Here, using antibodies to deplete TCR Vγ1⁺ cells, we saw that Vγ1⁺ γδ T cells were important for the control of PbXAT infection. Splenic Vγ1⁺ γδ T cells preferentially expand and express CD40L, and both Vγ1⁺ and Vγ4⁺ γδ T cells produce IFN‐γ during infection. Although expression of CD40L on Vγ1⁺ γδ T cells is maintained during infection, the IFN‐γ positivity of Vγ1⁺ γδ T cells is reduced in late‐phase infection due to γδ T‐cell dysfunction. In Plasmodium‐infected IFN‐γ signaling‐deficient mice, DC activation is reduced, resulting in the suppression of γδ T‐cell dysfunction and the dampening of γδ T‐cell expansion in the late phase of infection. Our data suggest that Vγ1⁺ γδ T cells represent a major subset responding to PbXAT infection and that the Vγ1⁺ γδ T‐cell response is dependent on IFN‐γ‐activated DCs.     

Galectin‐3 negatively regulates the frequency and function of CD4+CD25+Foxp3+ regulatory T cells and influences the course of Leishmania major infection

Galectin‐3, an endogenous glycan‐binding protein, plays essential roles during microbial infection by modulating innate and adaptive immunity. However, the role of galectin‐3 within the CD4⁺CD25⁺Foxp3⁺ T regulatory (T_REG) cell compartment has not yet been explored. Here, we found, in a model of Leishmania major infection, that galectin‐3 deficiency increases the frequency of peripheral T_REG cells both in draining lymph nodes (LNs) and sites of infection. These observations correlated with an increased severity of the disease, as shown by increased footpad swelling and parasite burden. Galectin‐3‐deficient (Lgals3^?/?) T_REG cells displayed higher CD103 expression, showed greater suppressive capacity, and synthesized higher amounts of IL‐10 compared with their wild‐type (WT) counterpart. Furthermore, both T_REG cells and T effector (T_EFF) cells from Lgals3^?/? mice showed higher expression of Notch1 and the Notch target gene Hes‐1. Interestingly, Notch signaling components were also altered in both T_REG and T_EFF cells from uninfected Lgals3^?/? mice. Thus, endogenous galectin‐3 regulates the frequency and function of CD4⁺CD25⁺Foxp3⁺ T_REG cells and alters the course of L. major infection.     

Plasmodium vivax infection alters the peripheral immunoregulatory network of CD4 T follicular cells and B cells

Regulatory and effector cell responses to Plasmodium vivax, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations. Here, we describe peripheral CD4⁺ T- and B-cell populations during and shortly after an uncomplicated P. vivax infection in 38 continuously exposed adult Amazonians. Consistent with previous observations, we found an increased frequency in CD4⁺CD45RA⁻CD25⁺FoxP3⁺ T regulatory cells that express the inhibitory molecule CTLA-4 during the acute infection, with a sustained expansion of CD21⁻CD27⁻ atypical memory cells within the CD19⁺ B-cell compartment. Both Th1- and Th2-type subsets of CXCR5⁺ICOS^hiPD-1⁺ circulating T follicular helper (cTfh) cells, which are thought to contribute to antibody production, were induced during P. vivax infection, with a positive correlation between overall cTfh cell frequency and IgG antibody titers to the P. vivax blood-stage antigen MSP1₁₉. We identified significant changes in cell populations that had not been described in human malaria, such as an increased frequency of CTLA-4⁺ T follicular regulatory cells that antagonize Tfh cells, and a decreased frequency of circulating CD24^hiCD27⁺ B regulatory cells in response to acute infection. In conclusion, we disclose a complex immunoregulatory network that is critical to understand how naturally acquired immunity develops in P. vivax malaria.     

Homeostatic regulation of CD8+ T cells after antigen challenge in the absence of Fas (CD95)

The role of Fas in the homeostatic regulation of CD8⁺ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) αβ transgenes specific for the LCMV glycoprotein peptide aa 33–41 in the context of H-2D^b were used. Five main results emerged: first, development of lymphadenopathy and of CD4⁻CD8⁻ double-negative B220⁺ T cells in lpr mice was not inhibited by the αβ TCR transgenes; second, tolerance induction and peripheral deletion of CD8⁺ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down-regulation of Fas-deficient TCR-transgenic CD8⁺ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8⁺ effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally susceptible to activation-induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4⁻CD8⁻ double-negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8⁺ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas.     

Early recruitment of natural CD4+Foxp3+ Treg cells by infective larvae determines the outcome of filarial infection

Human helminth infections are synonymous with impaired immune responsiveness indicating suppression of host immunity. Using a permissive murine model of filariasis, Litomosoides sigmodontis infection of inbred mice, we demonstrate rapid recruitment and increased in vivo proliferation of CD4⁺Foxp3⁺ Treg cells upon exposure to infective L3 larvae. Within 7 days post‐infection this resulted in an increased percentage of CD4⁺T cells at the infection site expressing Foxp3. Antibody‐mediated depletion of CD25⁺ cells prior to infection to remove pre‐existing ‘natural’ CD4⁺CD25⁺Foxp3⁺ Treg cells, while not affecting initial larval establishment, significantly reduced the number of adult parasites recovered 60 days post‐infection. Anti‐CD25 pre‐treatment also impaired the fecundity of the surviving female parasites, which had reduced numbers of healthy eggs and microfilaria within their uteri, translating to a reduced level of blood microfilaraemia. Enhanced parasite killing was associated with augmented in vitro production of antigen‐specific IL‐4, IL‐5, IL‐13 and IL‐10. Thus, upon infection filarial larvae rapidly provoke a CD4⁺Foxp3⁺ Treg‐cell response, biasing the initial CD4⁺ T‐cell response towards a regulatory phenotype. These CD4⁺Foxp3⁺ Treg cells are predominantly recruited from the ‘natural’ regulatory pool and act to inhibit protective immunity over the full course of infection.     

CD4+ Foxp3+ regulatory T‐cell number increases in the gastric tissue of C57BL/6 mice infected with Helicobacter pylori

Helicobacter pylori (H. pylori), one of the most common infections, is associated with various clinical outcomes. In addition to inducing inflammation, immunological clearance of the pathogen is often incomplete. Regulatory T cells (Treg cells) have been recently demonstrated to play an important role in H. pylori infection and the final clinical outcome. The aim of this study was to investigate the number and localization of CD4⁺Foxp3⁺ Treg cells in stomachs and spleens of H. pylori‐infected mice. The expression levels of Foxp3 as well as anti‐ and pro‐inflammatory cytokines before and after H. pylori triple eradication therapy were examined. We found that the percentages of CD4⁺Foxp3⁺ Treg cells out of the lamina propria lymphocytes (LPLs) and spleen lymphocytes in the infection group were higher than the PBS negative control group and the treatment group. H. pylori antigen stimulation was associated with an increased number of Treg cells in vitro. Furthermore, compared with the PBS and treatment groups, a higher mRNA expression level of Foxp3 in the gastric tissue was detected in the infection group. IL‐10 and TGF‐β1 contents were increased significantly in the culture supernatant of spleen lymphocyte stimulated with H. pylori antigen. A marked elevation in serum IFN‐γ level was observed in H. pylori‐infected mice. In addition, gastric tissues of the infection group contained more Foxp3⁺ cells. These results indicate that the percentage of CD4⁺Foxp3⁺ Treg cells are increased in H. pylori‐infected mice, suggesting a role of Treg cells in H. pylori‐induced pathologies, even at the early stages of chronic gastritis and gastric tumorigenesis.     

Involvement of CD8+ T cells in protective immunity against murine blood‐stage infection with Plasmodium yoelii 17XL strain

When developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8⁺ T cells contribute to protective immunity against infection with blood‐stage parasites of Plasmodium yoelii. Infection of C57BL/6 mice with P. yoelii 17XL was lethal, while all mice infected with a low‐virulence strain of the parasite 17XNL acquired complete resistance against re‐infection with P. yoelii 17XL. However, the host mice transferred with CD8⁺ T cells from mice primed only with P. yoelii 17XNL failed to acquire protective immunity. On the other hand, the irradiated host mice were completely resistant to P. yoelii 17XL infection, showing no grade of parasitemia when adoptively transferred with CD8⁺ T cells from immune mice that survived infection with both P. yoelii XNL and, subsequently, P. yoelii 17XL. These protective CD8⁺ T cells from immune WT mice had the potential to generate IFN‐γ, perforin (PFN) and granzyme B. When mice deficient in IFN‐γ were used as donor mice for CD8⁺ T cells, protective immunity in the host mice was fully abrogated, and the immunity was profoundly attenuated in PFN‐deficient mice. Thus, CD8⁺ T cells producing IFN‐γ and PFN appear to be involved in protective immunity against infection with blood‐stage malaria.     

B-cell activation in the mesenteric lymph nodes of resistant BALB/c mice infected with the murine nematode parasite Trichuris muris

Immune responses in resistant BALB/c mice infected with the murine nematode parasite Trichuris muris were examined. Following the establishment of infection, worm burdens of T. muris were expelled by BALB/c mice by day 21 postinfection (p.i.). Specific immunoglobulin G₁ (IgG₁) antibodies to T. muris excretory/secretory (E/S) antigens were detected in sera from infected mice, though specific IgG_2a antibodies were not observed during infection. Ig-producing cells increased in the mesenteric lymph nodes (MLN) of infected mice on days 7, 14, and 21 p.i., with the greatest increase in numbers of IgG- and IgA-producing cells occurring on day 14. Marked increases in the relative percentages of B220⁺ and surface Ig⁺ (sIg⁺) cells were observed in the MLN of infected mice on days 14 and 21 p.i. Furthermore, cellular expansion of the MLN in infected mice resulted in an increase in the absolute numbers of B220⁺ and sIg⁺ cells. The levels of interleukin 2 (IL-2), IL-4, and interferon-γ (IFN-γ) detected in the supernatants from concanavalin A-stimulated MLN cells of infected mice were higher than those found in normal mice. Consequently, the expulsion of T. muris in resistant BALB/c mice was concomitant with cytokine production and B-cell activation in the MLN of infected mice. These results suggest the involvement of B-cell responses in protective immunity to T. muris infection. Received: 12 May 1998 / Accepted: 5 August 1998     

Sequential appearance of γ/δ- and α/β-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes

To search for a potential role of T cell antigen receptor (TcR) γ/β-bearing cells in host-defense against Listeria monocytogenes, we analyzed the sequential appearance of γ/δ and α/β T cell in the peritoneal exudate cells (PEC) during an i.p. infection with sublethal dose (2 × 10³) of viable Listeria organisms in mice. The PEC on day 1 after the infection consisted of 48% macrophages and 50% lymphocytes, most of which were surface IgM⁺ (B) cells. The number of PEC increased to the maximal level by day 3. The PEC at this stage contained an appreciable number of CD3⁺ T cells in addition to a large number of macrophages. Of the CD3⁺ cells, the proportion of CD4^?CD8^? cells, most of which expressed no TcR α/β, increased to the maximal level on day 3 after the infection. In correlation with an increased number of CD3⁺CD4^?CD8^?TcR α/β^? cells, high level of TcR γ/δ chain gene messages was detected in the nonadherent population of the PEC on this stage. On the other hand, the PEC on day 8 contained an increased number of CD4⁺CD8^? and CD4^?CD8⁺ cells which expressed TcR α/β chain on their surface. These results suggest that the γ/δ T cells precede the α/β T cells in appearance during listerial infection. The γ/β T cells may be involved at the first line of the host-defense against Listeria.     

T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patients

About 10% of people infected with Mycobacterium tuberculosis develop active tuberculosis (TB), and Th1 effector cells and Th1 cytokines play key roles in controlling M. tuberculosis infection. Here, we hypothesise that this susceptibility to M. tuberculosis infection is linked to increased T regulatory (Treg) cells and Th2 cytokines in TB patients. To test this, we recruited 101 participants (71 TB patients, 12 non-TB pulmonary diseases and 18 healthy subjects) and investigated Treg cells and Th1/Th2 cytokines in peripheral blood. CD4⁺CD25⁺ T cells and CD4⁺CD25⁺FoxP3⁺ T cells significantly increased and IL-5 dramatically decreased in TB patients relative to healthy subjects. CD8⁺CD28⁻ T cells, IFN-γ, TNF-α, IL-10 and IL-4 significantly increased in patients with culture and sputum smear-positive pulmonary TB (PTB(+)) compared with healthy subjects. CD4⁺CD25⁺FoxP3⁺ and CD8⁺CD28⁻ T cells significantly decreased in PTB(+) after one month of chemotherapy. CD4⁺, CD4⁺CD25⁺ and CD8⁺CD28⁺ T cells significantly increased in extra-pulmonary TB patients after one month of chemotherapy. These findings suggest that M. tuberculosis infection induces circulating CD4⁺CD25⁺FoxP3⁺ and CD8⁺CD28⁻ T cell expansion, which may be related to the progression of M. tuberculosis infection, and that the balance between effector immune responses and suppression immune responses is essential to control M. tuberculosis infection.     

Mycobacterium tuberculosis‐specific CD4+ T‐cell response is increased,and Treg cells decreased,in anthelmintic‐treated patients with latent TB

In many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. We investigated the potential impact of helminth infection on immune responses to Mycobacterium tuberculosis (Mtb) in patients with latent Mtb infection with or without helminth infection (Strongyloides or Schistosoma), and tested T‐cell responses before and after anthelmintic treatment. The study was performed in migrants resident in the United Kingdom, where reexposure and reinfection following anthelmintic treatment would not occur. The frequency of CD4⁺IFN‐γ⁺ T cells was measured following stimulation with Mtb Purified Protein Derivative or ESAT‐6/CFP‐10 antigen, and concentrations of IFN‐γ in culture supernatants measured by ELISA and multiplex bead array. Helminth infection was associated with a lower frequency of CD4⁺IFN‐γ⁺ T cells, which increased following treatment. Patients with helminth infection showed a significant increase in CD4⁺FoxP3⁺ T cells (Treg) compared to those without helminth infection. There was a decrease in the frequency of Treg cells, and an associated increase in CD4⁺IFN‐γ⁺ T cells after the anthelmintic treatment. Here, we show a potential role of Treg cells in reducing the frequency and function of antimycobacterial CD4⁺IFN‐γ⁺ T cells, and that these effects are reversed after anthelmintic treatment.