Abstract
CD4(+) T cells are implied to sustain CD8(+) T-cell responses during persistent infections. As CD4(+) T cells are often themselves antiviral effectors, they might shape CD8(+) T-cell responses via help or via controlling antigen load. We used persistent murine CMV (MCMV) infection to dissect the impact of CD4(+) T cells on virus-specific CD8(+) T cells, distinguishing between increased viral load in the absence of CD4(+) T cells and CD4(+) T-cell-mediated helper mechanisms. Absence of T-helper cells was associated with sustained lytic MCMV replication and led to a slow and gradual reduction of the size and function of the MCMV-specific CD8(+) T-cell pool. However, when virus replication was controlled in the absence of CD4(+) T cells, CD8(+) T-cell function was comparably impaired, but in addition CD8(+) T-cell inflation, a hallmark of CMV infection, was completely abolished. Thus, CD8(+) T-cell inflation during latent CMV infection is strongly dependent on CD4(+) T-cell helper functions, which can partially be compensated by ongoing lytic viral replication in the absence of CD4(+) T cells.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adoptive Transfer
-
Animals
-
Antigens, Viral / immunology
-
CD4 Antigens / genetics
-
CD4 Antigens / immunology
-
CD4 Antigens / metabolism
-
CD4-Positive T-Lymphocytes / immunology*
-
CD4-Positive T-Lymphocytes / metabolism
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism
-
Cytomegalovirus Infections / immunology*
-
Cytomegalovirus Infections / virology
-
Flow Cytometry
-
Fluorescent Antibody Technique
-
Histocompatibility Antigens Class II / genetics
-
Histocompatibility Antigens Class II / immunology
-
Histocompatibility Antigens Class II / metabolism
-
Immunologic Memory / immunology*
-
Interleukin-2 Receptor alpha Subunit / genetics
-
Interleukin-2 Receptor alpha Subunit / immunology
-
Interleukin-2 Receptor alpha Subunit / metabolism
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Muromegalovirus / immunology
-
Muromegalovirus / physiology
-
Receptors, Interleukin-21 / genetics
-
Receptors, Interleukin-21 / immunology
-
Receptors, Interleukin-21 / metabolism
-
Virus Latency / immunology*
-
Virus Replication / immunology
Substances
-
Antigens, Viral
-
CD4 Antigens
-
Histocompatibility Antigens Class II
-
Interleukin-2 Receptor alpha Subunit
-
Receptors, Interleukin-21