Human T‐lymphotropic virus type 1 (HTLV‐1) is the agent of the HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may occur in >5% of patients during their lifetime. HTLV‐1‐infection causes disturbances in the immune system, and the viral load may also play an important role in the pathogenesis of HAM/TSP. Some cytokines are involved in the pathogenesis of this disorder. We have determined IL‐2, IL‐4, IL‐10, IL‐12 p70, IFN‐γ and TNF‐α production among HTLV‐1‐infected subjects from our HTLV‐out Clinic in Institute of Infectious ‘Emílio Ribas’ in Sao Paulo city, Brazil. PBMC obtained from healthy controls (n = 32), asymptomatic HTLV‐1 carriers (n = 68) and HAM/TSP patients (n = 44) were grown in the absence and in the presence of phytohaemagglutinin (PHA), and the supernatants’ fluids were measured for cytokines production. IL‐2 levels were increased in the asymptomatic HTLV‐1 carriers, and IFN‐γ was increased in both groups of patients (asymptomatic HTLV‐1 carriers and more significantly among HAM/TSP patients). IL‐4, IL‐10, TNF‐α and IL‐12 p70 levels were not significantly increased on both groups of patients, as compared with controls. The major finding of this study is that IFN‐γ was an important cytokine for the HAM/TSP pathogenesis. Therefore, immune modulation of IFN‐γ may be critical to treat of HAM/TSP patients.

No abstract

Although human T-cell lymphotropic virus type 2 (HTLV-2) is considered of low pathogenicity, serological diagnosis is important for counseling and monitoring. The confirmatory tests most used are Western blot (WB) and PCR. However, in high-risk populations, about 50% of the indeterminate WB were HTLV-2 positives by PCR. The insensitivity of the WB might be due to the use of recombinant proteins of strains that do not circulate in our country. Another possibility may be a high level of immunosuppression, which could lead to low production of virus, resulting in low stimulation of antibody. We found one mutation, proline to serine in the envelope region in the position 184, presented at least 1/3 of the samples, independent the indeterminate WB profile. In conclusion, we found no correlation of immune state, HTLV-2 proviral load, or env diversity in the K55 region and WB indeterminate results. We believe that the only WB kit available in the market is probably more accurate to detect HTLV-1 antibodies, and some improvement for HTLV-2 detection should be done in the future, especially among high-risk population.

The present study evaluated the in vitro response to different mitogens and a candidin antigen (CMA) in Human T‐cell lymphotropic virus type 1 (HTLV‐1) and co‐infected HIV‐1/HTLV‐1 patients, to identify if this co‐infection may modify the spontaneous lymph proliferative response. Peripheral blood mononuclear cells from 72 healthy seronegative controls, 75 asymptomatic HTLV‐1‐infected carriers, 42 HAM/TSP cases, 33 solely HIV‐1‐infected subjects and 24 HIV‐1/HTLV‐1 patients were assayed in the presence and absence of mitogens (PHA, PWM and OKT3) and CMA. The HAM/TSP group had the highest proliferation rate at 3 and 6 days after culture. HAM/TSP cases showed decreased response to PHA, compared with asymptomatic HTLV‐1 subjects, and most important, the co‐infected HIV‐1/HTLV‐1 cases presented a similar response to HTLV‐1‐infected subjects after 3 days of culture. The singles HIV‐1‐infected group had decreased in vitro response. It appears that during co‐infection, the HTLV‐1 regulatory proteins overwhelm the action of HIV‐1 regulatory proteins.

SUMMARYIntroduction: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4 + cell counts, thus rendering this parameter useless as an AIDS-defining event. Objective: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4 + cells. Material and Methods: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB) or polymerase chain reaction (PCR). All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO) classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC) classification of 1988. The first T CD4+ cells count available before starting antiretroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. Results: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4 + cell counts was 189 (98-688) cells/mm 3 and 89 (53-196) cells/mm 3 for co-infected subjects who had an AIDSdefining event, and HIV-only infected individuals, respectively (p = 0.036). Eight of 27 co-infected subjects (30%) were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4 + cell counts at the time of their AIDS-defining event. Discussion: Our results indicate that higher T CD4 + cells count among HIV-1/HTLV-1-coinfected subjects was found in 12% of the patients who presented an AIDS-defining event. These subjects also showed a TSP/HAM simile picture when it was the first manifestation of disease; this incidence is 20 times higher than that for HTLV-1-only infected subjects in endemic areas.