Antiviral protection by CD8+ versus CD4+ T cells. CD8+ T cells correlating with cytotoxic activity in vitro are more efficient in antivaccinia virus protection than CD4-dependent IL.
T cell-mediated protection against a recombinant vaccinia virus was evaluated in mice with respect to the relative contributions of CTL vs that of T cell-dependent IL and of CD4+ cells. H-2b mice primed with the wildtype of vesicular stomatitis virus serotype Indiana (VSV-IND wt) mount an in vitro measurable cytotoxic response against the nucleoprotein (NP) of VSV-IND and are protected against a challenge infection with a vaccinia-VSV recombinant virus expressing the NP of VSV-IND (vacc-IND-NP). Their protective mechanism was highly susceptible to in vivo depletion of CD8+ T cells, but resistant to CD4+ depletion or treatment with anti-IFN-gamma and anti-TNF-alpha. Surprisingly, also VSV-CTL nonresponder H-2k mice were protected against a challenging infection with vacc-IND-NP when primed with VSV-IND wt. In contrast to the CTL responder H-2b mice, this protection was highly susceptible to CD4+ T cell depletion and to anti-IFN-gamma or anti-TNF-alpha treatment, but resistant to CD8+ T cell depletion. Antibodies were not responsible because they failed to transfer protection; in contrast CD4+ T cells conferred significant protection. VSV-CTL responder H-2b and nonresponder H-2k mice were protected almost equally well against a challenge dose of 10(3) pfu vacc-IND-NP inoculated intracerebrally. However, after intracerebral challenge with 5 x 10(6) pfu vacc-IND-NP, the CTL nonresponder mice died, whereas the CTL responder mice eliminated the virus by day 5. These results collectively show that CD4+ T cell-dependent IL may mediate antiviral protection, but their efficiency is relatively weak compared with CD8-mediated protection correlating with cytotoxic activity in vitro.
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Institute of Pathology, University of Zürich, Switzerland.
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D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D000939:Epitopes; D006183:H-2 Antigens; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma