Abstracts (complete list) - Wissenschaft Online

Savita Nair, Ulf Dittmer
Role of CD4 + T cells in acute Friend Retroviral infections
Retroviruses are extremely pathogenic microbes and have accounted for significant
mortality and morbidity worldwide. Cytotoxic T lymphocytes (CTLs) are efficient in
keeping the viral replication under control during acute phase of infections but lose their
protective function during later stages under the suppressive effect of Regulatory T
cells. As a result of this, the virus manages to escape immune surveillance to cause
persistent infections for life. In life-threatening infections such as Human
Immunodeficiency virus (HIV) or Human T-cell leukemia virus (HTLV-1) immune escape
becomes critical. Role of CTLs is well defined in various retroviral infection models but
role of CD4 + T helper cells in retroviral immunity is poorly understood. Hence, we aimed
at characterising the function of CD4 + T cells during the initial phase of infections using
the Friend retrovirus (FV) murine infection model. FV infection causes lethal leukemia in
most strains of mice and the mouse model helps in studying the basic mechanisms of
immunological control and escape in both acute and persistent retroviral infections. In
vivo depletion of CD4 + T cells in acutely infected FV resistant mice strain demonstrated
that CD4 + T cells are important in controlling viral replication in acute FV infections and
onset of erythroleukemia. An ex vivo MHC-II tetramer kinetic analysis of FV-specific CD4
+ T cell responses during acute FV infection showed that maximal activation of CD4 + T
cells are achieved at 10 days post infection correlating with a decrease in viral loads.
Most significantly, FV-specific CD4 + T cells adoptively transferred into mice acutely
infected with FV showed that the transferred cells specifically recognised the FV antigen
in vivo, got activated to express an effector phenotype and produced the anti-viral
cytokine IFN-γ resulting in decreased viral loads. These results indicate that CD4 + T cell
response is vital for the control of virus replication during acute FV infection and for the
resistance of certain mouse strains to virus–induced disease.