Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals.

Abstract

CD4+ T cells of patients with AIDS exhibit a qualitative defect in their ability to respond to soluble antigen while their responses to mitogens remain normal. CD4+ T cells can be broadly divided phenotypically into "naive" [CD45RA+ (2H4+)] and "memory" [CD29+ (4B4+) or CD45RO+ (UCHL1+)] cell subpopulations, which represent distinct maturation stages. To determine the human immunodeficiency virus type 1 (HIV-1) infectability of memory and naive CD4+ T-cell subsets in vitro and to determine the in vivo preference of HIV-1 in these subpopulations, we obtained highly purified CD4+ T-cell subsets from normal and HIV-1-infected individuals and studied them by viral cultivation, quantitative polymerase chain reaction, and functional assays. Polymerase chain reaction studies demonstrated that the memory cell subset of CD4+ T cells is preferentially infected (4- to 10-fold more than naive T cells) by HIV-1 in vitro, and these memory cells are the principal reservoir for HIV-1 within CD4+ T cells obtained from infected individuals. Functional abnormalities attributable to CD4+ T cells in HIV-infected individuals (failure to respond in vitro to soluble antigen or to anti-CD3 monoclonal antibodies) were shown to reside primarily within these memory cells. Thus, the present study suggests that the selective functional defects present in the memory CD4+ T-cell subset of HIV-infected individuals may be a direct result of the preferential infection and consequently greater viral burden within these cells.

Differential requirements for HIV-1 replication in naive and memory CD4 T cells from asymptomatic HIV-1 seropositive carriers and AIDS patients

“…A recent report by Sehnittman et al [8] lends supporting evidence to a preferential infeeiion of memory subsets (four to lO-fold viral DNA in memory CD4 T cells) in HIV-1-infeeted individuals. Our results with PHA-)-1 L-2 tend to agree with the report of these authors.…”

“…detectable levels of p24 antigen in naive CD4 T cells from ASC patients were never observed before completion of phenotypic conversion of CD45RA'"*'^ cells into CD45RA-celis. It can be argued that virai replication occurs only after naive celis have at ieast partiaily switched to memory celis and as virai burden is lower in naive cells [8], detection of p24 antigens in supernatants probably requires more cycies of reinfection. Since cell stimulation is necessary to obtain viral replication and since it invariably results in a switch from naive to memory celis, which in HIV-1-infected CD4 cells does not differ from normal CD4 celis [9], a definitive answer to this question cannot be provided.…”

“…A wide range of immunologicai abnormalities observed during HIV infection has been attributed to a selective dysfunction and destruction of the memory subsets of CD4 T cells, which have a higher viral burden than naive subsets [8] and preferentially replicate HIV afler phytohaemagglutinin (PHA) slimulalion [9], Additionally, we have recently reported an important functional impairment of naive CD4T cells concerning their proliferative and cytokine secretion abilities [10].…”

Testes de contato e HIV: avaliação comparativa quanto à confiabilidade dos resultados

“…De acordo com Schnittman et al e Pericle et al, a função de memória é amplamente comprometida pela infecção dos linfócitos CD4+ pelo HIV. 15,18 Um número menor de células de Langerhans, que são apresentadoras de antígenos, tem sido encontrado na pele de pacientes com Aids. Tal fato pode estar associado com apresentação e processamento alterados dos antígenos alergênicos, contribuindo para a potencial incapacidade de reação imunomediada.…”

“…13 Porém, o contexto imunoló-gico de alguns pacientes infectados pelo HIV é complexo, já que muitos podem desenvolver mecanismos erráticos de resposta imunológica, tanto pela disfunção qualitativa dos linfócitos e da liberação de mediadores bioquímicos como por situações de reconstituição imunológica recentemente vislumbradas e ocasionadas pelo uso de antiretrovirais potentes. [14][15][16] A ocorrência de DCA em pacientes soropositivos para o HIV foi pouco estudada até o momento, e os testes de contato, principal instrumento para a confirmação do diagnóstico dessa doença, não foram avaliados cientificamente nesse grupo de pacientes.…”