T cell receptor usage in patients with non-progressing HIV infection

Abstract

SUMMARY It is still unclear why some patients with HIV progress more slowly than others to developing full blown AIDS. In this study using flow cytometry we have investigated the TCRBV repertoire of peripheral blood T lymphocytes in 17 long‐term non‐progressing HIV patients (LTNP) to determine if there is a biased usage of T cell receptor V gene products. Patients were identified from hospital records and entered into the study. Three colour flow cytometry was used to determine the expression of the TCRBV3S5, BV5S1, BV5S2, BV5S3, BV6S1, BV7S1, BV9, BV11, BV12, BV13, BV14, BV16, BV17, BV18, BV20, BV21S3, BV22, and BV23 by CD8 and CD4 positive cells isolated from the peripheral blood of patients and controls. Increases in the absolute numbers of CD8+ T cells expressing TCRBV2 and 8 were observed in the HIV‐LTNP population (P < 0·05 in both cases). No differences were seen in numbers of CD8+ T cells expressing other TCRBV or in any TCRBV within the CD4+ T cell popu‐lation. At follow up (1–2 years later), those patients in which CD4 levels were below 500 × 106/l were those initially found to have lower levels of TCRBV8 +ve CD8 cells. A significant increase in the absolute numbers of T cells coexpressing the gamma delta (γδ) T cell receptor and CD8 were also seen in the HIV‐LTNP patients compared with controls (P = 0·002). The increase in CD8+ T cells in the HIV‐LTNP patients may be interpreted as either an antigen specific, or group of antigen specific responses to viral antigen, or less likely a viral superantigen. A low level of TCRBV8, CD8+ T cells might be predictive of a more rapid disease progression and might indicate a protective role for this population in HIV infected patients. The increase in γδT cells bearing the CD8 coreceptor suggests a role for this cell type in the response to HIV infection.

A nonsense mutation (428G→A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection

“…However some infected individuals remain asymptomatic for a long period and these are called long-term non-progressors (LTNP) [12]. Typically for these patients are more than 7 years of documented HIV infection, a stable, normal CD4þ cell count over time, no symptoms of HIV-induced disease, low levels of HIV virus in the peripheral blood and no history of antiretroviral treatment [13].…”

Predicting the Impact of CD8+T Cell Polyfunctionality on HIV Disease Progression

“…Values of Ͻ1 usually indicate the beginning of the AIDS phase. Around 0.5 to 22% of CD8 ϩ T cells are HIV specific (35), meaning that the frequency of HIV-specific CD8 ϩ T cells among all lymphocytes is between 0.17 ϫ 10 Ϫ2 and 7.5 ϫ 10 Ϫ2 , assuming that 40% of all lymphocytes are CD4 ϩ T cells (36). Taking the maximum frequency of 0.075, the number of HIV-specific CD8 ϩ T cells per mm 3 of blood, E, is roughly 225 cells.…”

“…The frequency (or density) of HIV-specific CD8 ϩ T cells, E, is parameterized based on the CD4/CD8 ratio observed in HIVinfected individuals (34)(35)(36). The ratio of CD4 ϩ to CD8 ϩ T cells before the AIDS phase is of the order of 1.1 to 1.2 (34).…”

Flow cytometry evaluation of the T-cell receptor Vβ repertoire among human T-cell lymphotropic virus type-1 (HTLV-1) infected individuals: Effect of interferon alpha therapy in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

“…In with mobilization of a restricted mono-oligoclonal TCR repertoire during acute infection generally experience a rapid progression to AIDS, whereas a slower disease progression was associated with a broader TCR repertoire [12,13]. Alterations in certain TCR Vh members are also detected in long-term non-progressors [14]. However, in HTLV-1 infection, there has been no study with regard to the TCR-V usage between infected individuals and normal healthy uninfected controls (NCs).…”