Tumorous proliferations of plasmacytoid dendritic cells and Langerhans cells associated with acute myeloid leukaemia

Song H‐L, Huang W‐Y, Chen Y‐P & Chang K‐C
(2012) Histopathology  61, 974–983 Tumorous proliferations of plasmacytoid dendritic cells and Langerhans cells associated with acute myeloid leukaemia Aims: Proliferation of plasmacytoid dendritic cells (PDCs) occurs in both reactive lymphoid hyperplasia and myeloproliferative disorders, especially chronic myelomonocytic leukaemia. PDCs in the former appear reactive, but in the latter are reported to be clonally related to the underlying myeloid neoplasm. Langerhans cells (LCs), another type of dendritic cell, also proliferate in both reactive dermatoses and, rarely, myeloproliferative disorders, such as acute leukaemia. Methods and results: We report a rare case of tumorous proliferation of PDCs and LCs in the systemic lymph nodes in a 55‐year‐old man with acute myeloid leukaemia. A microsatellite instability assay showed identical patterns of short tandem repeats in both microdissected PDC and LC components, along with blood blasts. Conclusions: We hypothesize that the combined proliferations of PDCs and LCs derive from the same haematopoietic stem cells, but that they differentiate divergently under the effect of different microenvironments.     

Mapping of the lingual immune system reveals the presence of both regulatory and effector CD4+ T cells

Background Sublingual immunotherapy (SLIT) is safe and reduces both symptoms and medication requirements in patients with type I respiratory allergies. Nonetheless, immune mechanisms underlying SLIT need to be further documented. Objective A detailed characterization of the lingual immune system was undertaken in mice, to investigate the presence of tolerogenic and pro‐inflammatory mechanisms. Methods Immune cells were characterized in lingual tissues from BALB/c mice using immunohistology and flow cytometry. Resident CD4⁺ T cells were sorted and toll‐like receptor (TLR) expression profiles as well as functional characterization were assessed by RT‐PCR, T cell suppressive assays and cytokine gene expression, respectively. Results Eosinophils and mast cells were only detected in submucosal tissues. No NK, NK‐T, γ/δ, CD8⁺ T cells, nor B‐lymphocytes were detected. Potential antigen presenting cells include various subsets of dendritic cells (CD207⁺ Langerhans cells, CD11b⁺CD11c⁺ myeloid cells and 120G8⁺ plasmacytoid DCs) together with F4/80⁺ macrophages. Noteworthy, both CD103^? and CD103⁺ CD4⁺ T cells expressing TLR2 and TLR4 receptors are present along the lamina propria, in vicinity of myeloid CD11b⁺CD11c^± dendritic cells. Such resident lingual CD4⁺ T lymphocytes comprise both suppressive T cells as well as cells with memory/effector functions (i.e. expressing IFNγ, IL4, IL10 and IL17 genes following stimulation), irrespective of the presence of the mucosal addressing marker CD103. Conclusion The sublingual route is pertinent to induce antigen‐specific tolerance, due to (i) limited numbers of pro‐inflammatory cells, rather located in submucosal tissues, (ii) co‐localization of APCs and resident CD4⁺ T cells with regulatory functions. Since the oral immune system can also elicit pro‐inflammatory effector responses, the cytokine milieu in which allergens are presented by sublingual APCs needs to be controlled during immunotherapy (e.g. with adjuvants) in order to favour tolerance over inflammation.     

Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma

Huang C, Sun Z, Sun Y, Chen X, Zhu X, Fan C, Liu B, Zhao Y & Zhang W
(2012) Histopathology  60, 793–803 Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma Aims: We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC). Methods and results: We studied the expression of CypA, CD147, hypoxia‐inducible factor 1α (HIF‐1α), vascular endothelial growth factor A and C (VEGF‐A and VEGF‐C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF‐1α, VEGF‐A and VEGF‐C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P < 0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF‐1α, VEGF‐A and VEGF‐C. A significant relationship between VEGF‐A and VEGF‐C was also detected (P < 0.01). Patients with overexpression of CypA, CD147, HIF‐1α and VEGF‐C had significantly worse overall survival (P < 0.05) using Kaplan–Meier analysis. Multivariate Cox regression analysis showed that HIF‐1α, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients. Conclusions: The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.     

Esophageal epithelium of women with AIDS: Thickness and local immunity

The aim of this study was to evaluate the morphological characteristics of the esophageal epithelium (EE) and its local immunity. Esophageal fragments of autopsied women were collected from 1980 to 2008, and two groups were analyzed: with AIDS (n=17) and without AIDS (n=12). The measurement of the esophageal epithelium was carried out through the image analysis software ImageJ, and the immunostaining of Langerhans cells (LCs) was carried out using anti-S100 antibody. Women with AIDS, when compared with women without AIDS, had significantly thinner EE (220.6 versus 243.5 μm), a less number of LCs (6.2 versus 18.8 LCs/mm²), and a higher percentage of immature or morphologically altered LCs (66.6 versus 40.0%). The malnourished women, when compared with normonourished women, regardless of AIDS, had significantly thinner EE (227.1 versus 238.0 μm) and a less number of LCs (6.2 versus 12.5 LCs/mm²). The percentage of immature or morphologically altered LCs was the same in both groups. Additionally, the women with AIDS (7.0 versus 2.8%) and the malnourished women (5.8 versus 3.1%) presented a significantly higher percentage of fibrosis. We concluded that AIDS and malnutrition contribute to the decrease in esophagus local immunity and, therefore, to a possible increase in local opportunistic infections.     

Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin

Summary: Langerhans cells (LCs) are antigen-presenting dendritic cells (DCs) that reside in epithelia. The best studied example is the LC of the epidermis. By electron microscopy, their identifying feature is the unique rod- or tennis racket-shaped Birbeck granule. The phenotypic hallmark is their expression of the C-type lectin receptor langerin/CD207. Langerin, however, is also expressed on a recently discovered population of DC in the dermis and other tissues of the body. These ‘dermal langerin⁺ dendritic cells’ are unrelated to LCs. The complex field of langerin-negative dermal DCs is not dealt with here. In this article, we briefly review the history, ontogeny, and homeostasis of LCs. More emphasis is laid on the discussion of functional properties in vivo. Novel models using genetically engineered mice are contributing tremendously to our understanding of the role of LCs in eliciting adaptive immune responses against pathogens or tumors and in inducing and maintaining tolerance against self antigens and innocuous substances in vivo. Also, innate effector functions are increasingly being recognized. Current activities in this area are reviewed, and possibilities for future exploitation of LC in medicine, e.g. for the improvement of vaccines, are contemplated.     

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

Yoo S H, Lee K, Chae J Y & Moon K C
(2011) Histopathology  58 , 191–197
CD151 expression can predict cancer progression in clear cell renal cell carcinoma Aims: CD151 is known to be implicated in cancer progression and metastasis. The aim was to evaluate the expression of CD151 in clear cell renal cell carcinoma (CCRCC) and to assess its prognostic significance. Methods and results: The expression of CD151 was evaluated in 489 cases of CCRCC by immunohistochemistry. Immunoreactivity was classified into four categories (minimal, 0–10% positive cells; focal, 10–50% positive cells; diffuse moderate, >50% positive cells with moderate staining intensity; diffuse strong, >50% positive cells with strong staining). To determine the statistical significance of CD151 expression in CCRCC, all cases were divided into two groups based on their CD151 expression level: a CD151‐low group (n = 257; minimal and focal) and a CD151‐high group (n = 232; diffuse). Expression of CD151 was correlated positively with pT, pN, pM categories, pathological tumour–node–metastasis (pTNM) stage, nuclear grade, tumour size and patient’s age. The CD151‐high group had significantly shorter cancer‐specific survival (P < 0.001) and progression‐free survival (P < 0.001) times. Furthermore, multivariate analysis showed that CD151 expression was an independent predictor for tumour progression in patients with CCRCC (P = 0.040). Conclusions: High CD151 expression is associated with advanced stage and high nuclear grade in CCRCC. CD151 is a prognostic marker for tumour progression in CCRCC patients.     

Characterization of the immunological microenvironment of tumour buds and its impact on prognosis in mismatch repair-proficient and -deficient colorectal cancers

Zlobec I, Minoo P, Terracciano L, Baker K & Lugli A
(2011) Histopathology 59 , 482–495
Characterization of the immunological microenvironment of tumour buds and its impact on prognosis in mismatch repair‐proficient and ‐deficient colorectal cancers Aims: Tumour budding in colorectal cancer is established as a poor prognostic factor. The inverse correlation of tumour buds with peritumoural lymphocytic inflammation suggests an interaction with specific immune responses. The aims of this study were to characterize the immunological microenvironment of tumour buds and its impact on prognosis in mismatch repair (MMR)‐proficient and ‐deficient colorectal cancers. Methods and results: A total of 297 colorectal cancers were double‐immunostained for CK22 plus one of the following: CD138, CD16, CD20, CD21, CD56, CD68, CD8, forkhead box P2 (FoxP3), granzyme B, mast cell tryptase, CD3 or T cell intracellular antigen‐1 (TIA)‐1. Tumour buds and immune cells within the region of densest budding were evaluated [×40 high‐power field (HPF)] simultaneously. In both MMR‐proficient and ‐deficient cancers, CD8⁺, FoxP3⁺ and CD68⁺ cells were observed most frequently (>40 cells/HPF) and were independent prognostic factors. A combined prognostic score of tumour budding and CD8⁺, FoxP3⁺ and CD68⁺ distinctly identified patients with low‐, moderate‐ or high‐risk colorectal cancers with 5‐year survival rates of 75.2% [confidence interval 95% (CI): 66–83], 56.3% (95% CI: 43–68) and 25.2% (95% CI: 14–38), respectively, in MMR‐proficient and ‐deficient cancers. Conclusion: The combined assessment of tumour budding with CD8, FoxP3 and CD68 lymphocytes could represent a basis for a prognostic score similar to the Bloom Richardson grade (BRE) and Gleason scores for breast and prostatic cancers.     

Neoangiogenesis in laryngeal carcinoma: angiogenin and CD105 expression is related to carcinoma recurrence rate and disease-free survival

Marioni G, Marino F, Blandamura S, D’Alessandro E, Giacomelli L, Guzzardo V, Lionello M, de Filippis C & Staffieri A
(2010) Histopathology 57 , 535–543
Neoangiogenesis in laryngeal carcinoma: angiogenin and CD105 expression is related to carcinoma recurrence rate and disease‐free survival Aims: Angiogenin regulates angiogenesis supporting primary and metastatic tumour growth. CD105 is a proliferation‐associated protein expressed in angiogenic endothelial cells. The aim of this study was to investigate for the first time angiogenin expression in laryngeal squamous cell carcinoma (LSCC) and to evaluate the relationship between angiogenin and CD105 expression, clinicopathological and prognostic parameters. Methods and results: A total of 108 consecutive operable LSCCs were studied. Angiogenin expression was determined immunohistochemically in both carcinoma cells and intratumoral vessels. CD105 expression was evaluated in endothelial cells of LSCC and calculated by a computer‐based image analysis system. The percentage of the fields occupied by CD105‐assessed microvessels was determined. Angiogenin expression in carcinoma cells was higher in LSCC patients who experienced loco‐regional recurrence of disease (P = 0.032). Disease‐free survival (DFS) was shorter in cases with carcinoma cells showing angiogenin expression >21.0% (P = 0.035). Angiogenin expression in carcinoma cells was correlated strongly with the angiogenin score in endothelial cells of intratumoral vessels (P = 0.0000). Higher loco‐regional carcinoma recurrence rate and shorter DFS in patients with high CD105 expression were found (P = 0.0004, P = 0.0001). Conclusions: Angiogenin expression in laryngeal carcinoma cells and CD105 expression can be considered as potentially useful to detect LSCC patients with higher risk of disease recurrence who might benefit from more aggressive therapy.     

A case of pulmonary cryptococcosis with non-small cell lung cancer in idiopathic CD4+ T-lymphocytopenia

Cryptococcus neoformans commonly causes opportunistic infections in immunocompromised patients, especially in patients with AIDS. CD4+ T-lymphocytopenia in AIDS indicates an increased risk of opportunistic infection and a decline in immunological function. Idiopathic CD4 T-lymphocytopenia (ICL) is characterized by depletions in the CD4+ T-cell subsets, without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, and T-cell subsets should be evaluated in patients who present with unusual opportunistic infections. We report a case of pulmonary cryptococcosis and lung cancer in a patient with persistently low CD4+ cell counts, without evidence of HIV infection.     

Antibody-dependent cellular cytotoxicity (ADCC)-mediated destruction of human immunodeficiency virus (HIV)-coated CD4+ T lymphocytes by acquired immunodeficiency syndrome (AIDS) effector cells

The acquired immunodeficiency syndrome (AIDS) is defined in clinical terms by the development of Kaposi's sarcoma and/or severe opportunistic infections in persons without predisposing conditions. A hallmark of the syndrome has been a decrease in the number of CD4⁺ T helper cells. The reduction in the frequency of the CD4⁺ lymphocytes has been postulated to be primarily the result of human immunodeficiency virus (HIV) tropism and cytophathogenicity for the T-cell subset. Yet only a small percentage of cells is actually infected with HIV. Recently, we provided evidence indicating that AIDS patients' natural killer cells can mediate normal levels of antibody-dependent cellular cytotoxicity (ADCC) despite exhibiting a defect in natural killer (NK) effector function (J Immunol 139:55, 1987). This finding prompted us to investigate whether AIDS patients' effector cells could mediate ADCC against circulating CD4⁺ T cells infected with or expressing HIV antigen. The findings reported herein demonstrate that AIDS effector cells can mediate lysis of CEM (CD4⁺ T-cell line) coated with HIV protein in the presence of HIV-specific antibody. Lysis was specific, as non-HIV-coated CEM or the addition of HIV-negative serum resulted in no lysis. We then examined HIV-coated peripheral blood-derived CD4⁺ T lymphocytes as targets in ADCC. We demonstrate that in the presence of HIV-specific antibody, HIV-coated CD4⁺ T lymphocytes serve as targets for ADCC by AIDS effector cells. The lytic activity obtained with AIDS effector cells was comparable to that obtained with normal effector cells. These results demonstrate that AIDS effector cells can mediate ADCC against HIV-coated CD4⁺ T lymphocytes and suggest that ADCC may play a rolein vivo in the pathogenesis of AIDS.     

Follicular dendritic cells in follicular lymphoma and types of non-Hodgkin lymphoma show reduced expression of CD23, CD35 and CD54 but no association with clinical outcome

Jin M K, Hoster E, Dreyling M, Unterhalt M, Hiddemann W & Klapper W
(2011) Histopathology  58 , 586–592
Follicular dendritic cells in follicular lymphoma and types of non‐Hodgkin lymphoma show reduced expression of CD23, CD35 and CD54 but no association with clinical outcome Aims: Follicular dendritic cells (FDC) are specialized antigen‐presenting cells found exclusively in the germinal centre (GC), which can be detected in B cell non‐Hodgkin lymphomas (NHL) as reactive bystander cells. Recently, gene expression profiling has revealed that FDC networks might be associated with clinical outcome in follicular lymphoma. The aim was to characterize FDC in NHL and to evaluate a possible association with outcome in follicular lymphoma. Methods and results: The extent and immunophenotype of FDC was determined semi‐quantitatively in reactive GC and NHL (follicular lymphoma, angioimmunoblastic T cell lymphoma, mantle cell lymphoma) using fluorescence double staining and digital image analysis. In all NHL tested CD23 and CD35 and CD54 were expressed at relatively low levels on FDC, comparable to FDC found in the dark zone of the GC. However, the extent of FDC networks did not correlate with the clinical outcome of 102 patients with follicular lymphomas treated within a prospectively randomized trial. Conclusions: FDC found in different types of NHL show quantitatively reduced expression of several proteins, suggesting that there are functional differences between FDC in normal GC and NHL. The extent of the FDC networks in follicular lymphoma is not useful as a prognostic marker.     

CD56 (NCAM) expression in ameloblastomas and other odontogenic lesions

Cairns L, Naidu A, Robinson C M, Sloan P, Wright J M & Hunter K D
(2010) Histopathology 57, 544–548
CD56 (NCAM) expression in ameloblastomas and other odontogenic lesions Aims: Ameloblastomas recapitulate certain elements of tooth formation. CD56 is expressed by a variety of cells and is used in tumour diagnosis, but is also expressed in the enamel organ during tooth development. The aim of this study was to describe the expression of CD56 in odontogenic lesions with particular reference to the differential diagnosis of ameloblastoma and odontogenic keratocyst. Methods: Cases were selected from the pathology archives at Glasgow Royal Infirmary, Glasgow, Royal Victoria Infirmary, Newcastle and Department of Diagnostic Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas. The study population included 38 ameloblastomas, 19 odontogenic keratocysts and a number of other odontogenic lesions, including nine compound odontomes. All sections were examined for CD56 immunoreactivity and the extent of staining was recorded. Results: Thirty‐seven of 38 (97%) ameloblastomas expressed CD56 on the cell membrane of peripheral cells in tumour nests (16 extensively, 21 focally). Immunoreactivity was lost in areas of inflammation, acanthomatous differentiation, in areas of cystic change and upon fusion with overlying surface epithelium. One odontogenic keratocyst expressed CD56 (5%, P < 0.0001). CD56 was expressed very focally in two odontomes, exclusively in stratum intermedium‐like cells. Conclusions: CD56 expression in odontogenic epithelium is highly suggestive of ameloblastoma and can help in differentiating this from odontogenic keratocyst.     

Therapeutic potential of CAMPATH-1H in skeletal tumours

Fritsche‐Guenther R, Gruetzkau A, Noske A, Melcher I, Schaser K‐D, Schlag P M, Kasper H‐U, Krenn V & Sers C
(2010) Histopathology 57, 851–861 Therapeutic potential of CAMPATH‐1H in skeletal tumours Aims: CD 52 is a glycosylphosphatidylinositol (GPI)‐anchored glycoprotein that is expressed abundantly on all lymphocytes, monocytes, macrophages, eosinophils and in the male genital tract. To date, the physiological role of CD52 on lymphocytes has not been elucidated. However, an antibody directed to CD52 called CAMPATH‐1H has been shown to be capable of depleting lymphocytes. The aim of this study was to analyse tissue and cell lines of non‐neoplastic bone, cartilage and skeletal tumours for CD52 expression. Methods and results: The expression of CD52 mRNA and protein both in vivo and in vitro was detected. Malignant tumours showed higher CD52 expression compared to benign tumours, suggesting a role in the development and progression of bone tumours. Interestingly, immunohistochemistry and flow cytometry revealed that CD52 was expressed not only on the surface of tumour cells, but also in the cytoplasm. The results obtained in osteosarcoma cells showed that CAMPATH‐1H leads to a complement‐independent reduction of viable cells. Conclusion: CD52 is expressed in a variety of bone tumours and the in vitro studies presented herein suggest that CAMPATH‐1H treatment might have therapeutic potential for osteosarcoma patients.     

Diarrhea, CD4+ cell counts and opportunistic protozoa in Indian HIV-infected patients

The aim of this study was to examine the relationships among diarrhea, CD4⁺ cell counts and opportunistic protozoa in HIV-infected patients in North India. In a retrospective study, blood and stool samples of 200 HIV-infected patients from March 2001 until 2003, submitted to the AIDS division of National Institute of Communicable Diseases (NICD), were analyzed. Each patient was examined for opportunistic protozoa, HIV-1 status and CD4⁺ cell counts, and screened for diarrheal symptoms. The rate of diarrhea was 38% in the stool examination. In HIV-infected patients in the groups CD4⁺ > 500 cells/L, 200 cells/L < CD4⁺ < 500 cells/L and in the AIDS patients CD4⁺ < 200 cells/L, diarrhea was 14.7, 29.8 and 56.1%, respectively. It is clear that the diarrhea in the AIDS patients was significant compared with the two former groups (P < 0.0005). In the AIDS patients CD4⁺ < 200 cells/L with diarrhea, Cryptosporidium infection was, at 56.5%, the highest and statistically significant compared with the other parasites (P = 0.037). Microsporidium was detected in 30.4% of the AIDS patients. Diarrhea was common and most strongly associated in patients with low CD4⁺ cell counts. The data stress the importance of opportunistic protozoa in the HIV-infected patients, and that opportunistic protozoa should be expected in HIV-infected patients with low CD4⁺ and diarrhea.     

Langerhans cells promote early germinal center formation in response to Leishmania‐derived cutaneous antigens

Efficient formation of early GCs depends on the close interaction between GC B cells and antigen‐primed CD4⁺ follicular helper T cells (T_FH). A tight and stable formation of T_FH/B cell conjugates is required for cytokine‐driven immunoglobulin class switching and somatic hypermutation of GC B cells. Recently, it has been shown that the formation of T_FH/B cell conjugates is crucial for B‐cell differentiation and class switch following infection with Leishmania major parasites. However, the subtype of DCs responsible for T_FH‐cell priming against dermal antigens is thus far unknown. Utilizing a transgenic C57BL/6 mouse model designed to trigger the ablation of Langerin⁺ DC subsets in vivo, we show that the functionality of T_FH/B cell conjugates is disturbed after depletion of Langerhans cells (LCs): LC‐depleted mice show a reduction in somatic hypermutation in B cells isolated from T_FH/B cell conjugates and markedly reduced GC reactions within skin‐draining lymph nodes. In conclusion, this study reveals an indispensable role for LCs in promoting GC B‐cell differentiation following cutaneous infection with Leishmania major parasites. We propose that LCs are key regulators of GC formation and therefore have broader implications for the development of allergies and autoimmunity as well as for future vaccination strategies.     

Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy: potential role in mesangial matrix expansion

Ikezumi Y, Suzuki T, Karasawa T, Hasegawa H, Yamada T, Imai N, Narita I, Kawachi H, Polkinghorne K R, Nikolic‐Paterson D J & Uchiyama M
(2011) Histopathology  58, 198–210
Identification of alternatively activated macrophages in new‐onset paediatric and adult immunoglobulin A nephropathy: potential role in mesangial matrix expansion Aims: New onset of the clinical symptoms of immunoglobulin A (IgA) nephropathy (IgAN) manifests with proliferative glomerular lesions in children, whereas adults exhibit mesangial matrix expansion and interstitial fibrosis. Alternatively, activated (M2) macrophages have been implicated in promoting tissue fibrosis in some settings. Therefore, the aim of this study was to investigate whether M2 macrophages are present in new‐onset IgAN and if they are related to pathological differences between paediatric and adult disease. Methods and results: Biopsy specimens from paediatric (<10 years, n = 14; >12 years, n = 15) and adult (n = 27) IgAN showed a significant infiltrate of CD68⁺ macrophages. M2 macrophages, identified by CD163 or CD204 expression, were detected in glomeruli and the interstitium, being more prominent in adults versus young children. CD163⁺ and CD204⁺ macrophages were present in areas of fibrosis containing myofibroblasts, and double staining showed that CD163⁺ cells produced the profibrotic molecule, connective tissue growth factor. In young children, total CD68⁺ macrophages, but not M2 macrophages, correlated with glomerular hypercellularity. In contrast, in adults and older children, mesangial matrix expansion correlated with M2 macrophages but not with the total CD68⁺ macrophage infiltrate. Conclusions: Alternatively activated M2 macrophages are present in new‐onset paediatric and adult IgAN, and this population may promote the development of fibrotic lesions.     

An atypical CD8 T‐cell response to Chlamydia muridarum genital tract infections includes T cells that produce interleukin‐13

Chlamydia trachomatis urogenital serovars D–K are intracellular bacterial pathogens that replicate almost exclusively in human reproductive tract epithelium. In the C. muridarum mouse model for human Chlamydia genital tract infections CD4 T helper type 1 cell responses mediate protective immunity while CD8 T‐cell responses have been associated with scarring and infertility. Scarring mediated by CD8 T cells requires production of tumour necrosis factor‐α (TNF‐α); however, TNF‐α is associated with protective immunity mediated by CD4 T cells. The latter result suggests that TNF‐α in‐and‐of itself may not be the sole determining factor in immunopathology. CD8 T cells mediating immunopathology presumably do something in addition to producing TNF‐α that is detrimental during resolution of genital tract infections. To investigate the mechanism underlying CD8 immunopathology we attempted to isolate Chlamydia‐specific CD8 T‐cell clones from mice that self‐cleared genital tract infections. They could not be derived with antigen‐pulsed irradiated naive splenocytes; instead derivation required use of irradiated immune splenocyte antigen‐presenting cells. The Chlamydia‐specific CD8 T‐cell clones had relatively low cell surface CD8 levels and the majority were not restricted by MHC class Ia molecules. They did not express Plac8, and had varying abilities to terminate Chlamydia replication in epithelial cells. Two of the five CD8 clones produced interleukin‐13 (IL‐13) in addition to IL‐2, TNF‐α, IL‐10 and interferon‐γ. IL‐13‐producing Chlamydia‐specific CD8 T cells may contribute to immunopathology during C. muridarum genital tract infections based on known roles of TNF‐α and IL‐13 in scar formation.