In humans, the circulating pool of mycobacteria-reactive Vγ9Vδ2+ T cells is expanded with age and may contribute to Mycobacterium tuberculosis immunosurveillance. We observed that two subsets of Vγ9Vδ2+ T cells could be identified on the basis of CD27 expression in immunocompetent adults, showing that functionally differentiated γδ T cells have lost CD27 expression. In contrast, the CD27−CD45RA−Vγ9Vδ2+ T cell subset of effector cells was absent in cord blood cells from healthy newborns and lacking in the peripheral blood from HIV-infected patients. Moreover, circulating Vγ9Vδ2+ T cell effectors were significantly reduced in patients with acute pulmonary tuberculosis, resulting in a reduced frequency of IFN-γ-producing cells after stimulation with nonpeptidic mycobacterial ligands. These observations indicate that monitoring and boosting γδ T cell effectors could be clinically relevant both in immunocompromised hosts and during active tuberculosis disease.

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV) strain. Analyses of T cell repertoires in health care workers who survived SARS-CoV infection during the 2003 outbreak revealed that their effector memory V gamma 9V delta 2 T cell populations were selectively expanded ~3 months after the onset of disease. No such expansion of their alpha beta T cell pools was detected. The expansion of the V gamma 9V delta 2 T cell population was associated with higher anti-SARS-CoV immunoglobulin G titers. In addition, in vitro experiments demonstrated that stimulated V gamma 9V delta 2 T cells display an interferon- gamma -dependent anti-SARS-CoV activity and are able to directly kill SARS-CoV-infected target cells. These findings are compatible with the possibility that V gamma 9V delta 2 T cells play a protective role during SARS.

Avian infl uenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease. The aim of this study was to evaluate the immune cross-reactivity between human and avian infl uenza (H5N1) strains in healthy donors vaccinated for seasonal infl uenza A (H1N1)/(H3N2). A small frequency of CD4 T cells specifi c for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells. We also observed that seasonal vaccination is able to raise neutralizing immunity against infl uenza (H5N1) in a large number of donors. No correlation between infl uenzaspecifi c CD4 T cells and humoral responses was observed. N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point. These fi ndings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian infl uenza A virus subtype H5N1 by seasonal infl uenza vaccination.

Summary γδ T lymphocytes recognize non‐peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non‐peptidic antigens was observed in human immunodeficiency virus‐positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of γδ T‐cell anergy in HIV+ patients with opportunistic infections/co‐infections (HIV‐OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on γδ T‐cell functions. Peripheral γδ T‐cell distribution and in vitro reactivity to a non‐peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. γδ T‐cell subset distribution was altered more in HIV‐OIC patients than in asymptomatic HIV+ subjects (HIV‐ASY). Specifically, the Vδ2/Vδ1 ratio was inverted as a consequence of a decrease in Vδ2 T‐cell number. Moreover, IPP‐stimulated Vδ2 T cells from the HIV‐OIC group displayed a major defect in interferon‐γ (IFN‐γ) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored γδ T‐cell function. Accordingly, in vitro CD45RA depletion resulted in γδ T‐cell hyporesponsiveness. Altogether, the incidence of γδ T‐cell anergy was increased in HIV‐OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore γδ T‐cell reactivity, extending the immune recovery to non‐peptidic microbial antigens.

Our results show a strict association between host immune competence and the severity of the clinical course of H1N1v infection. By monitoring host functional response, patients with an enhanced risk of developing influenza-associated severe complications could be identified in a timely manner.