Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy individuals.

Tissue-resident memory T cells (TRM) persist locally in nonlymphoid tissues where they provide frontline defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69, which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to reenter the circulation and potentially migrate to distant tissue sites has been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can down-regulate CD69 and exit the tissue. In addition, we identified a skin-tropic CD4+CD69-CD103+ population in human lymph and blood that is transcriptionally, functionally, and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can reenter circulation and migrate to secondary human skin sites where they reassume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.

Comparison and functional characterisation of peripheral blood mononuclear cells isolated from filarial lymphoedema and endemic normals of a South Indian population.

OBJECTIVE: The underlying problem in lymphatic filariasis is irreversible swelling of the limbs (lymphoedema), which is a unique feature of lymphatic insufficiency. It is still unclear whether the natural ability of lymphatics to form functional lymphatic vasculature is achieved or attenuated in the lymphoedemal pathology. Clinical studies have clearly shown that circulating lymphatic progenitors (CLPs), a subset of bone marrow-derived mononuclear cells (PBMCs), contribute to post-natal lymph vasculogenesis. CLP-based revascularisation could be a promising strategy to bypass the endothelial disruption and damage incurred by the filarial parasites. Thus our aim was to compare and characterise the functional prowess of PBMCs in physiological and lymphoedemal pathology. METHODS: PBMCs were isolated from venous blood sample from drug-naive endemic normals (EN) and drug-deprived filarial lymphoedema (FL) individuals using density gradient centrifugation. Adhesion, transwell migration and in vitro matrigel assays were employed to characterise the lymphvasculogenic potential of PBMCs. CLPs were phenotypically characterised using flow cytometry; expression levels of lymphatic markers and inflammatory cytokines were quantified using qRT-PCR and ELISA, respectively. RESULTS: PBMCs from FL group display poor adherence to fibronectin (P = 0.040), reduced migration towards SDF-1α (P = 0.035), impaired tubular network (P = 0.004) and branching point (P = 0.048) formation. The PBMC mRNA expression of VEGFR3 (P = 0.039) and podoplanin (P = 0.050) was elevated, whereas integrin α9 (P = 0.046) was inhibited in FL individuals; additionally, the surface expression of CD34 (P = 0.048) was significantly reduced in the FL group compared to the EN group. CONCLUSION: PBMCs from filarial lymphoedema show defective and dysregulated lymphvasculogenic function compared to endemic normals.

[The case of hairy cell leukosis in pediatrics].

According publications' data, hairy cell leukosis encounters in humans aged from 26 to 70 years and in males four times more often than in females. The disease is manifested by impotence, splenomegaly, and presence in blood and bone marrow clone of lymphoid cells with particular morphology, cytochemic markers and immune phenotype (sIg+, CD19+, CD20+, CD5-, CD10-, with marked expression of CD25+, CD103+). The presented clinical case of illness with hairy cell leucosis is the first one detected in pediatric practice in adolescent of 16 years old.

Haematological profile of 21 patients with hairy cell leukaemia in a tertiary care centre of north India.

BACKGROUND & OBJECTIVES: Hairy cell leukaemia (HCL) is a B cell neoplasm which constitutes around 2 per cent of all the lymphoid leukaemias. It has a characteristic morphology and immunophenotypic profile. It is important to distinguish HCL from other B cell lymphoproliferative disorders due to availability of different chemotherapeutic agents. This study presents clinical, haematological and immunophenotypic profile of patients with HCL seen over a period of four years in a tertiary care hospital in north India. METHODS: Twenty one cases of hairy cell leukaemia were analyzed for their clinical details, haemogram, bone marrow examination and immunophenotypic findings. RESULTS: Age of the patients ranged from 28-76 yr with male predominance. Weakness and fever were commonest presentations. Splenomegaly, hepatomegaly, lymphadenopathy were seen in decreasing order of frequency. Anaemia was noted in all 21 patients, leukopenia in 15 and thrombocytopenia in 19 cases. Fourteen patients were pancytopenic. Bone marrow examination showed typical hairy cells in all cases. Immunophenotyping showed expression of CD19, CD20, CD103, CD25 and CD11c in all cases, while positivity was seen for CD79b in 93.7 per cent, kappa light chain restriction in 60 per cent and lambda in 40 per cent cases. Notably, 20 per cent showed CD10 and 12 per cent showed CD23 expression. INTERPRETATION & CONCLUSIONS: This study reveals some unusual findings in otherwise classical disease entity, like absence of palpable spleen, presence of lymphadenopathy, normal or elevated leukocyte counts, expression of CD10, which at times could be diagnostically challenging.

Integrin α E ß 7 (CD103) expression in bronchoalveolar lymphocytes of patients with hypersensitivity pneumonitis.

PURPOSE: CD4+/CD8+ ratio in bronchoalveolar lavage fluid (BALF) often retrieves contradictory findings when used for diagnosis of sarcoidosis and hypersensitivity pneumonitis (HP), so CD103+ has been investigated as a possible differential marker. We aimed to compare CD103+ expression in BALF T-lymphocytes between patients with HP, sarcoidosis and other interstitial lung diseases (ILD). METHODS: An observational study carried out over a 2-year period included consecutive patients with suspected ILD who underwent BALF as part of their initial diagnostic work-up; CD103+ expression on BALF T-lymphocytes was evaluated. After a final diagnosis established according to international criteria, three patient subgroups-HP, ILD (which included idiopathic interstitial pneumonia and connective tissue disease-associated lung disorders) and sarcoidosis-were considered for further analysis. RESULTS: A total of 77 subjects were enrolled, 20 with HP, 16 with other ILD and 41 with sarcoidosis. A significantly higher number of CD4+ CD103+ and CD8+ CD103+ lymphocytes were found in HP patients. Among patients with sarcoidosis, 12 (29.3 %) presented a BALF CD4+/CD8+ <3.5, all of them with histological confirmation. Compared to these patients, also statistically significant higher CD4+ CD103+ counts in HP patients were observed (p = 0.007). Among HP patients, although bird fanciers (n = 14) presented higher percentages of both CD4+ CD103+ and CD8+ CD103+ T-lymphocytes than those with work-related HP (n = 5), the differences did not reach statistical significance. CONCLUSIONS: Patients with HP present significantly higher counts of CD103+ T-lymphocytes in BALF, both in the CD4+ and CD8+ subsets, when compared to sarcoidosis, even with sarcoidosis subgroup presenting a BALF CD4+/CD8+ <3.5. The expression of CD103 may help in the interpretation of BALF data in these diffuse granulomatous lung disorders.

The molecular signature of tissue resident memory CD8 T cells isolated from the brain.

Tissue resident memory (Trm) CD8 T cells represent a newly described memory T cell population. We have previously characterized a population of Trm cells that persists within the brain after acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm cells do not undergo recall expansion after dissociation from the tissue. Furthermore, these Trm cells do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells, we compared the gene expression profiles of Trm cells isolated from the brain with those of circulating memory T cells isolated from the spleen after an acute virus infection. Trm cells displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors, and overexpressed several inhibitory receptors. Cumulatively, these data indicate that Trm cells are a distinct memory T cell population disconnected from the circulating memory T cell pool and display a unique molecular signature that likely results in optimal survival and function within their local environment.

Evaluation of CD103 (αEß7) integrin expression by CD8 T cells in blood as a surrogate marker to predict cervical T cell responses in the female genital tract during HIV infection.

Mucosal homing receptors expressed by blood T cells may be useful surrogates for measuring mucosal T cell immune responses at the site of HIV transmission. Here, we investigated whether HIV-specific responses by T cells expressing the mucosal integrin receptor CD103 in blood reliably predicted corresponding HIV-specific responses at the cervix. The frequency of CD8+ T cells expressing CD103 in blood correlated significantly with the number of CD103+CD8+ T cells from the cervix suggesting that CD103 was involved in trafficking of T cells from blood to the cervical mucosa. TGF-ß concentrations in plasma were significantly associated with the frequency of CD103 expression by blood but not cervical CD8 T cells. The majority of Gag-responsive CD8 T cells were CD103+ in both blood and at the cervix. Despite this, the magnitude of Gag-specific IFN-γ responses by CD103+CD8+ T cells in blood did not predict similar Gag-specific responses at the cervix.

Deletion of the alpha8 integrin gene does not protect mice from myocardial fibrosis in DOCA hypertension.

BACKGROUND: In the heart, the alpha8 integrin chain is expressed in fibroblasts and vascular smooth-muscle cells but its functional role in the myocardium is unknown. Integrins can contribute to tissue fibrosis in several organs. We tested the hypothesis that alpha8 integrin-mediated cell-matrix interactions add to cardiac fibrotic alterations during hypertension. METHODS: Desoxycorticosterone-acetate (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the alpha8 integrin chain and wild-type mice. Histological and immunohistochemical evaluations were performed in heart tissue. RESULTS: Blood pressure was slightly higher in DOCA-treated alpha8 integrin-deficient mice compared to DOCA-treated wild types. Expression of alpha8 integrin and its ligands fibronectin and osteopontin was increased in the hearts of DOCA-treated wild types compared to salt-loaded controls. However, relative left ventricular weights did not differ between DOCA-treated wild types and alpha8 integrin-deficient mice. Moreover, expansion of collagen I immunoreactivity and cell proliferation was similar in both groups. The number of osteopontin-positive cells was not different in DOCA-treated alpha8 integrin-deficient and DOCA-treated wild-type mice. Despite of a comparable degree of fibrosis in both groups, alpha-smooth-muscle actin and discoidin domain receptor 2 (DDR2)-positive myofibroblasts were only detected in wild-type DOCA-treated mice, not in DOCA-treated alpha8 integrin-deficient mice. CONCLUSIONS: The results show that lack of alpha8 integrin does not reduce fibrotic changes in the hearts of DOCA-salt hypertensive mice. Our findings do not argue for a profibrotic effect of an increased alpha8 integrin expression in the myocardium in hypertension.

Blood monocyte subsets differentially give rise to CD103+ and CD103- pulmonary dendritic cell populations.

There are two major myeloid pulmonary dendritic cell (DC) populations: CD103+ DCs and CD11bhigh DCs. In this study, we investigated in detail the origins of both myeloid DC pools using multiple experimental approaches. We show that, in resting lung, Ly-6ChighCCR2high monocytes repopulated CD103+ DCs using a CCR2-dependent mechanism, and these DCs preferentially retained residual CCR2 in the lung, whereas, conversely, Ly-6ClowCCR2low monocytes repopulated CD11bhigh DCs. CX3CR1 was required to generate normal numbers of pulmonary CD11bhigh DCs, possibly because Ly-6Clow monocytes in the circulation, which normally express high levels of CX3CR1, failed to express bcl-2 and may have diminished survival in the circulation in the absence of CX3CR1. Overall, these data demonstrate that the two circulating subsets of monocytes give rise to distinct tissue DC populations.