Novel role of CD8(+) T cells and major histocompatibility complex class I genes in the generation of protective CD4(+) Th1 responses during retrovirus infection in mice.
CD4(+) Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8(+) T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2(b) allele at major histocompatibility complex (MHC) class II loci, a single H-2D(b) MHC class I allele was sufficient for the development of a CD4(+) Th1 response to FV. This effect of H-2D(b) on CD4(+) T-cell responses was dependent on CD8(+) T cells, as demonstrated by depletion studies. A direct effect of CD8(+) T-cell help in the development of CD4(+) Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponder H-2(a/a) mice induced FV-specific responses of H-2D(d)-restricted CD8(+) cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8(+) T cells to naive H-2(a/a) mice prior to infection resulted in the generation of FV-specific CD4(+) Th1 responses. This novel helper effect of CD8(+) T cells could be an important mechanism in the development of CD4(+) Th1 responses following vaccinations that induce CD8(+) CTL responses. The ability of MHC class I genes to facilitate CD4(+) Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.
Peterson
Karin E
KE
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Stromnes
Ingunn
I
Messer
Ron
R
Hasenkrug
Kim
K
Chesebro
Bruce
B
D000483:Alleles; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005622:Friend murine leukemia virus / Q000472:pathogenicity*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014412:Tumor Virus Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D006183:H-2 Antigens; D007371:Interferon-gamma