Gamma interferon responses of CD4 and CD8 T-cell subsets are quantitatively different and independent of each other during pulmonary Mycobacterium bovis BCG infection.
Gamma interferon (IFN-gamma) is a key cytokine in host defense against intracellular mycobacterial infection. It has been believed that both CD4 and CD8 T cells are the primary sources of IFN-gamma. However, the relative contributions of CD4 and CD8 T-cell subsets to IFN-gamma production and the relationship between CD4 and CD8 T-cell activation have not been examined. By using a model of pulmonary mycobacterial infection and various immunodetection assays, we found that CD4 T cells mounted a much stronger IFN-gamma response than CD8 T cells at various times after mycobacterial infection, and this pronounced IFN-gamma production by CD4 T cells was attributed to both greater numbers of antigen-specific CD4 T cells and a greater IFN-gamma secretion capacity of these cells. By using major histocompatibility complex class II-deficient or CD4-deficient mice, we found that the lack of CD4 T cells did not negatively affect primary or secondary CD8 T-cell IFN-gamma responses. The CD8 T cells activated in the absence of CD4 T cells were capable of immune protection against secondary mycobacterial challenge. Our results suggest that, whereas both CD4 and CD8 T cells are capable of IFN-gamma production, the former represent a much greater cellular source of IFN-gamma. Moreover, during mycobacterial infection, CD8 T-cell IFN-gamma responses and activation are independent of CD4 T-cell activation.
Ngai
Patricia
P
Department of Pathology and Molecular Medicine, McMaster University, 1200 Main St. West, Hamilton, Ontario L8N 3Z5, Canada.
McCormick
Sarah
S
Small
Cherrie
C
Zhang
Xizhong
X
Zganiacz
Anna
A
Aoki
Naoko
N
Xing
Zhou
Z
D000818:Animals; D000938:Antigen-Presenting Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
D007371:Interferon-gamma