T cells and the skin

In addition to its role as a mechanical barrier, the skin plays an important role in temperature regulation, vitamin D synthesis and absorption of ultraviolet radiation. The importance of the skin as an immunological organ was not fully appreciated until the advent of immunosuppressive agents such as cyclosporin and tacrolimus, which have a predominant action against T lymphocytes and have been found to be effective in the management of common skin diseases such as atopic eczema and psoriasis. T lymphocytes are of fundamental importance to the immune system. Access from the vascular compartment into the skin is facilitated by adhesion molecules located on the endothelial of dermal blood vessels. Selective upregulation of adhesion molecules occurs in various inflammatory skin diseases and specific skin homing T lymphocytes preferentially enter the skin rather than other organs. T cell have recently been classified into Th1 and Th2 cells based on their cytokine profile. Th1 cells produce interleukin 2 (IL-2) and interferon gamma, important in macrophage activation and cytotoxity, and Th2 cells produce IL-4 and IL-5, important in B cell maturation and humoral immunity. Contact dermatitis and psoriasis are characterised by Th1 cells and atopic dermatitis by Th2 cells. The Th1/Th2 profile is also important in infectious diseases such as leprosy in which polarisation towards tuberculoid or lepromatous disease depends on a predominance of Th1 or Th2 cells, respectively. Future management of diseases affecting the skin is likely to depend on a greater understanding of the infiltrating T cell subsets and appropriate modulation of the Th1 and Th2 profile.(AU)

HTLV-1 polymyositis

The case is described of an HTLV-1 seropositive Jamaican woman who presented with signs and symptoms of polymyositis and myelopathy. A muscle biopsy showed features of myositis with a mononuclear inflammatory infiltrate, variation in fibre size and evidence of regeneration. Immunocytochemistry showed the mononuclear cells were composed of macrophages and T-lymphocytes suggesting a cell-mediated response. Multiplex PCR demonstrated the presence of the HTLV-I tax gene within the muscle. (AU)

Immunological abnormalities in HTLV-1 infected Jamaican children (abstract)

This paper reports on the immunological findings of a case control study of 50 infective dermatitis (ID) patients and 36 atopic eczema (AE) patients undertaken between December 1990 and August 1991. It also reports on a comparison of these results with those of age and sex matched normal controls, and age and sex matched HTLV-I infected asymptomatic children. Investigations of their immune systems showed that both ID and AE patients had normal responses to delayed hypersensitivity skin tests, and normal compliment levels. However there was a marked increase in the activity of both T and B lymphocyte systems, with all immunoglobulin levels being significantly increased in ID patients versus others. The CD4:CD8 ratio was increased, with an increase in the CD4 counts. Monoclonal antibody tests showed increased T cell activation. The results confirm immune dysfunction though the precise mechanism of the immunodysregulation remains to be determined. (AU)

Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome

Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflamatory cells. Except in the vicinity of the worm, where the epithlium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intaepithelial T cells. There was also an increase in crypt epithelial cells proliferation. Lamina propia T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS. (AU)

Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis

Twelve long term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-I) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long term interlukin-2-dependent cell lines exhibited a pattern characteristic of CD4+ -activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50 percent of the cells exhibited HTLV-I antigens by IF. However numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high M-r polypeptides were detected by Western blot in cell lysates when comparing TSP-or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46. (AU)

Concurrent multicentric angiofollicular lymph node hyperplasia and peripheral T-cell lymphoma

Multicentric angiofollicular lymph node hyperplasia (MAFH) is a variant of Castleman's disease, localized angiofollicular lymph node hyperplasia. Unlike Castleman's disease, MAFH sometimes runs an aggressive clinical course culminating in death, mainly from infection and rarely from malignant lymphoma. The lymphoma may develop months or years after the onset of MAFH but may be present at the time of diagnosis. In this paper, we present a case of MAFH with co-existing peripheral T-cell lymphoma, in a 59 year-old man who died from disseminated disease. This adds another to the list of five such cases recorded in the literature since the recognition of MAFH (AU)

Transmission of HTLV-I and HIV among homosexual men in Trinidad

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15 percent vs 2.4 percent in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19 percent of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.(AU)

Racial and other characteristics of human T cell leukemia/lymphome (HTLV-1) and AIDS (HTLV-111) in Trinidad

Adult T cell leukaemia/lymphoma was first recognised as a clinical entity in southwest Japan. Subsequently the Caribbean has been found to be another area where the disease is endemic, and sporadic cases have been identified in different parts of the world. The human T cell leukaemia/lymphoma virus (HTLV-1) is causally related to adult T cell leukaemia/lymphoma. A sub-group of HTLV, designated HTLV-111, has recently been isolated from many patients with the acquired immunodeficiency syndrome (AIDS) and preAIDS, and there is now evidence that this variant is the primary cause of AIDS. This is the first report from Trinidad to describe twelve cases of adult T cell leukaemia/lymphoma and 14 of AIDS. All were in patients of African descent. No cases were seen in subjects of East Indian descent, who, like those of African descent, comprise as much as 40 percent of the population

Mononuclear cells in sickle cell disease: subpopulations and in vitro response to mitogens

The subpopulations of mononuclear cells and the lymphocyte proliferative capacity following mitogen stimulation were studied in 22 patients with homozygous sickle cell (SS) disease and 25 controls with a normal haemoglobin (AA) genotype. The total number of lymphocytes in peripheral blood samples was higher in SS patients compared to controls. Expressed as a percentage of total lymphocytes, the number of B lymphocytes (detected by membrane immunoglobulin Fluorescence) was normal and of T lymphocytes (identified by sheep erythocyte rosetting) was slightly reduced in SS disease. Expressed in absolute numbers, both B and T lymphoctes were increased. Lymphocyte proliferation measured by tritium labelled thymidine incorporation following stimulation with phytohaemaeglutin A and concanavalin A was normal. Following pokeweed mitogen stimulation, thymidine incorporation was significantly increased in SS disease although normal when expressed as a stimualtion index. These results do not suggest a major defect in cell mediated immunity in sickle cell disease. The number of circulating monocytes was increased in SS disease and correlated inversely with the number of reticulocyytes (r= -0.58, p < 0.005) (AU)

Human T-Cell leukaemia/lymphoma virus-associated lymphoreticular neoplasia in Jamaica

19 (34 percent ) of 56 Jamaicans with lymphoproliferative neoplasia had antibody to the human t-cell leukemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkin's lymphoma (NHL) or chronic lynphocytic leukemia. Of 16 consecutive patients presenting with NHL 11 (69 percent ) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukemia/lymphoma. HTLV-associated leukemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica (AU)

The human type-C retrovirus, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma

Type-C RNA tumour viruses have been implicated in the etiology of naturally occurring leukemias and lymphomas of animals. Human T-cell leukimia/lymphoma virus (HTLV) is the first human virus of this class consistently identified in association with a specific type of human leukemia/lymphoma. The isolation of HTLV was made possible by the ability to grow mature T-cell in tissue culture usually with T-cell growth factor (TCGF). We now report a cluster usually with T-cell leukemia/lymphoma among Blacks from the Caribbean in which all eight cases are positive for HLV virus and/or antibody. These patients have diseases that appears indistinguisable from Japanese adult T-cell leukemia/lymphoma which, as we have also reported, is associated with HTLV in over 90 percent of cases. The finding of HTLV antibodies in some of the normal population in the Caribbean and Japan, and the clustering of a specific form of T-cell leukemia/lyphoma in these virus-endemic areas, suggest that HTLV infection may be associated with the occurrence of a distinctive clinico-pathologic entity (Summary)