Wimalasundera, Sunethra S.; (1997) The characterisation of a T cell response to human rhinovirus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Most viral infections are controlled either by neutralising antibodies and/or cytolysis of infected cells by MHC class I restricted CD8 T cells. However, CD4 T cells may also contribute towards the defence against viral infections by the release cytokines which can either provide help for the differentiation of effector T and B cells or have a direct anti-viral effect on the infected cell. The T cell response induced by HRV has not yet been directly examined. The objective of this study was to understand the nature of the T cell response and its contribution to the pathogenesis of human rhinovirus (HRV) infection in humans. As a local lymphoid tissue to the upper respiratory tract, the tonsil provides a site of drainage for any antigen that enters via the nasopharyngeal surface. The high prevalence of HRV and the site of the tonsil would predict the presence of a recall or memory response to HRV in T cells derived from tonsils. The present study demonstrates that indeed a T cell proliferative response to HRV can be detected in tonsil derived T cells in approximately 80[percent] of the 132 individuals (mostly children aged between 4-14 years of age) tested. This response was found to be dependent on the presence of T cells and MHC class II+ cells and mediated predominantly by the CD4 T cell subset with underlying cytokine profile of ThI type cells. In most of the experiments only a single representative member of each viral subgroup was used although in a few tonsils a panel of 7 different serotypes comprising members of each group were tested. Evidence to suggest a recall or memory type response was suggested by the ability of these limited number of serotypes to induce a response in the large majority of individuals and also by the ability to induce a response within 3-4 days in culture. However, surprisingly HRV as well as influenza A (IFZ A) was able to induce a recall type response in both the CD45RA and CD45RO T cell subsets but were unable to activate umbilical cord blood derived mononuclear cells (UCBMC). In a limited number of experiments the HRV response in peripheral blood (PB) derived T cells was examined and shown to compare both quantitatively and qualitatively with tonsil derived T cells. A population with antigen presenting capacity was shown to exist in an 80-90[percent] CD3 enriched responder population which could only be removed after MHC class II depletion. Sequential depletion of various subsets from the stimulator population suggested that these may be dendritic cells (DC). Thus, the present study suggests that in contrast to most viral infections, HRV induces predominantly a MHC class II restricted CD4 T cell response in vitro. The induction of CD4 ThI cells could provide defence against primary infection by controlling viral replication via cytokines such as IFN[gamma] and TNF[alpha] and provide protection against reinfection by supporting the production of neutralising antibodies by B cells. The ability to induce comparable HRV specific responses in both CD45RA and CD45RO T cells suggest that the CD45RA T cells may be primed T cells reverted from CD45RO to CD45RA.

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