CD4+ T cells are required for the priming of CD8+ T cells following infection with herpes simplex virus type 1.
The role of CD4(+) helper T cells in modulating the acquired immune response to herpes simplex virus type 1 (HSV-1) remains ill defined; in particular, it is unclear whether CD4(+) T cells are needed for the generation of the protective HSV-1-specific CD8(+)-T-cell response. This study examined the contribution of CD4(+) T cells in the generation of the primary CD8(+)-T-cell responses following acute infection with HSV-1. The results demonstrate that the CD8(+)-T-cell response generated in the draining lymph nodes of CD4(+)-T-cell-depleted C57BL/6 mice and B6-MHC-II(-/-) mice is quantitatively and qualitatively distinct from the CD8(+) T cells generated in normal C57BL/6 mice. Phenotypic analyses show that virus-specific CD8(+) T cells express comparable levels of the activation marker CD44 in mice lacking CD4(+) T cells and normal mice. In contrast, CD8(+) T cells generated in the absence of CD4(+) T cells express the interleukin 2 receptor alpha-chain (CD25) at lower levels. Importantly, the CD8(+) T cells in the CD4(+)-T-cell-deficient environment are functionally active with respect to the expression of cytolytic activity in vivo but exhibit a diminished capacity to produce gamma interferon and tumor necrosis factor alpha. Furthermore, the primary expansion of HSV-1-specific CD8(+) T cells is diminished in the absence of CD4(+)-T-cell help. These results suggest that CD4(+)-T-cell help is essential for the generation of fully functional CD8(+) T cells during the primary response to HSV-1 infection.
Rajasagi
Naveen K
NK
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Kassim
Sadik H
SH
Kollias
Christina M
CM
Zhao
Xiangyi
X
Chervenak
Robert
R
Jennings
Stephen R
SR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005802:Genes, MHC Class II; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma