p16(INK4a) Expression and Immunologic Aging in Chronic HIV Infection

Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16(INK4a) (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls. Results showed that untreated HIV-infected subjects exhibited increased per-cell p16 protein expression that was discordant with chronological aging. ART restored p16 protein expression to levels comparable with HIV-negative subjects in the CD4 compartment, but not in CD8 T cells, which can be an indicative of an irreversible activation/exhaustion status on these cells. Additionally, the frequency of activated CD4+ and CD8+ T cells was positively correlated with p16 expression in CD4+ and CD8+ T cells in untreated subjects. In contrast to healthy controls, untreated HIV-infected individuals had increased p16 levels within the effector memory (T-EM) subset, indicating a possible role for this marker in impaired clonal expansion during antiviral effector function. Taken together, these data demonstrate that chronic HIV infection is associated with elevated expression of the cellular aging marker p16 in T cells. ART restored normal p16 levels in the CD4+ T cell compartment, indicating that use of therapy can be of fundamental importance to normal cell cycling and maintaining immune homeostasis

Uso do anticorpo monoclonal OKT3 em rejeiçöes graves / Use of OKT3 monoclonal antibody in grave rejections

Com o objetivo de avaliar a reposta ao anticorpo monoclonal OKT3 nas rejeiçöes celulares graves, estudamos 14 pacientes com rejeiçöes resistentes a tratamento com pelo menos uma pulsoterapia, 13 dos quais apresentando biópsia renal prévia. Cinco deles eram receptores de rim de cadáver e nove de doador vivo. Os adultos receberam 5mg de OKT3 e as crianças 2,5mg por dez dias. A monitorizaçäo de células T3 foi realizada em nove pacientes. Onze pacientes tiveram revertido o episódio de rejeiçäo; nos outros três casos, em que näo houve resposta, os rins foram perdidos: dois por vasculopatia aguda e um por rejeiçäo celular. Um deles apresentou reversäo parcial com posterior perda por vasculopatia. Dos 11 pacientes que tiveram o episódio revertido, 10 foram biopsiados previamente e apresentavam: RCA em quatro casos, RCA e NTA em três RCA e VAT em outros três. Em cinco pacientes que apresentavam vasculopatia, o OKT3 foi capaz de reverter o episódio em três ocasiöes. Os dois casos sem resposta tratavam-se de um quarto transplante com três perdas imunológicas prévias e um paciente com prova cruzada antilinfócitos B e antimonócitos positiva. Apenas um caso de RCA pura näo respondeu ao tratamento, provavelmente por se tratar de paciente com cross-match histórico positivo contra linfócitos T e anti-B e monócitos atuais positivos. A reversäo dos quadros de RCA pura foi igual a 87,5%. No total, incluindo as rejeiçöes com componente vascular, a taxa de reversäo foi de 78%. Concluímos que o OKT3 é um potente imunossupressor, capaz de reverter rejeiçöes graves, inclusive muitas das que se apresentam com componente vascular importante. É uma arma terapêutica que näo deve ser descartada nos casos de vasculopatia aguda do transplante

[Study of a sub-population of T-lymphocytes with the HLA-DR molecule in rheumatoid polyarthritis]. / Etude d'une sous-population T lymphocytaire à molécules HLA-DR dans la polyarthrite rhumatoïde.

The sub-population of T-lymphocytes which express the DR antigen was studied in 48 patients with rheumatoid arthritis and in 42 controls. The sub-population of T-lymphocytes which express DR was found to be larger in the patients with rheumatoid arthritis. This increase is even more marked in cases of rheumatoid arthritis with high erythrocyte sedimentation rates and with a high level of immune complexes.